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How long does immunity to influenza last when contracting the disease vs vaccination

How long does immunity to influenza last when contracting the disease vs vaccination



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The long term efficacy of flu vaccines are well documented, however I cannot seem to find a good source showing how long immunity lasts when contracting the disease.

I suspect it can't be much longer than vaccines since the virus mutates so quickly.


The effect on adaptive immunity are often stronger when contracting the flu than for getting the flu vaccination. The backside of this is that the flu is a quite dangerous disease which could end fatally, so getting the vaccine is always preferrable.

Getting infected by a specific flu strain (or receive a vaccination against it) generates specific immunity against this strain. If it mutates to strong or you get infected with another strain, you will have no immunity (and will have to develop a new immune response.

It seems that immunity against the flu can be livelong (against this strain) after you went through an infection and survived it. There are two studies showing long term response against antigens from the 1918 flu pandemic. The first (summarized in reference 1, the original article is reference 2) shows specific antibodies against the reconstructed haemagglutinin protein (H1) from the 1918 virus strain.

Serum from people born 1915 or before showed specific activity against this virus antigen, even more than 90 years after the infection.

The second study analyzes cross-reactivity of antibodies against the 2009 A/H1N1 pandemic flu strain. Here the cross reactivity of people born before 1930 was the highest - the 1918 strain (with which these people most likely had contact) was also a H1N1 virus. Although these viruses mutated between 1918 und 2009, there is still enough similarity that they are recognized by H1N1 specific antibodies (see reference 2).

A study which compared antibodies responses of people who contracted the 2009 flu against people who where vaccinated against it, showed that the antibody response was more longlasting in the people who got the infection (see reference 3).

So I think it is safe to say that the immune response is stronger after the infection compared to the vaccination, but the vaccination is much safer.

References:

  1. How Long Does Flu Immunity Last?
  2. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors
  3. Antibody Dynamics of 2009 Influenza A (H1N1) Virus in Infected Patients and Vaccinated People in China

Covid-19 immunity likely lasts for years

NIH

Covid-19 patients who recovered from the disease still have robust immunity from the coronavirus eight months after infection, according to a new study. The result is an encouraging sign that the authors interpret to mean immunity to the virus probably lasts for many years, and it should alleviate fears that the covid-19 vaccine would require repeated booster shots to protect against the disease and finally get the pandemic under control.

“There was a lot of concern originally that this virus might not induce much memory,” says Shane Crotty, a researcher at the La Jolla Institute for Immunology in California and a coauthor of the new paper. “Instead, the immune memory looks quite good.”

The study, published January 6 in Science, contrasts with earlier findings that suggested covid-19 immunity could be short-lived, putting millions who’ve already recovered at risk of reinfection. That predicament wouldn’t have been a total surprise, since infection by other coronaviruses generates antibodies that fade fairly quickly. But the new study suggests reinfection should only be a problem for a very small percentage of people who’ve developed immunity—whether through an initial infection or by vaccination.

In fact, the new study does show that a small number of recovered people do not have long-lasting immunity. But vaccination ought to offset that problem by ensuring herd immunity in the larger population.

The new paper studied blood samples from 185 men and women who had recovered from covid-19—most from a mild infection, although 7% were hospitalized. Each person provided at least one blood sample between six days and eight months after their initial symptoms, and 43 of the samples were taken after six months. The team that ran the investigation measured the levels of several immunological agents that work together to prevent reinfection: antibodies (which tag a pathogen for destruction by the immune system or neutralize its activity), B cells (which make antibodies), and T cells (which kill infected cells).

The researchers found that antibodies in the body declined moderately after eight months, although levels varied wildly between individuals. But T-cell numbers declined only modestly, and B-cell numbers held steady and sometimes inexplicably grew. That means that despite decreases in free-flowing antibodies, the components that can restart antibody production and coordinate an attack against the coronavirus stick around at pretty high levels. Crotty adds that the same mechanisms that lead to immune memory after infection also form the basis for immunity after vaccination, so the same trends ought to hold for vaccinated people as well.

And while immunity to other coronaviruses has been less than stellar, it’s worth looking at what happens in people who recovered from SARS, a close cousin of the virus that causes covid-19. A study published in August showed that T cells specific to SARS can remain in the blood for at least 17 years, bolstering hopes that covid-19 immunity could last for decades.

The new study isn’t perfect. It would have been better to collect multiple blood samples from every participant. “Immunity varies from person to person, and uncommon individuals with weak immune memory still may be susceptible to reinfection,” Crotty cautions. And we can’t make any firm conclusions about covid-19 immunity until years have passed—it’s simply too early. Nonetheless, this latest result is a good indication that if the vaccination rollout goes well (a big if), we might soon be able to put the pandemic behind us.


Getting a flu shot every year? More may not be better

I f you’ve been diligent about getting your flu shot every year, you may not want to read this. But a growing body of evidence indicates that more may not always be better.

The evidence, which is confounding some researchers, suggests that getting flu shots repeatedly can gradually reduce the effectiveness of the vaccines under some circumstances.

That finding is worrying public health officials in the US, who have been urging everyone to get a flu shot each year — and who still believe an annual vaccination is better than skipping the vaccines altogether.

Dr. Edward Belongia is among the scientists who have seen the picture coming into focus. He and some colleagues at Wisconsin’s Marshfield Clinic Research Foundation reported recently that children who had been vaccinated annually over a number of years were more likely to contract the flu than kids who were only vaccinated in the season in which they were studied.

“The vaccine was significantly more effective … if they had not been vaccinated in the previous five years,” Belongia, an epidemiologist, recounted in a recent interview with STAT.

Vaccines work by exposing the immune system to a part of a disease agent — in the case of influenza, to two proteins on the exterior of the viruses — that has been rendered harmless. The vaccines tell the immune system to be ready to mount an offensive if it encounters the specified invaders.

The immune system then produces stores of protective ammunition — antibodies — it can use to fight off infection.

With many vaccines, an additional dose or two boosts the levels of antibodies in a person’s body. Some vaccines actually require multiple doses to be effective.

So the fact that repeated vaccination against flu might diminish rather than enhance the vaccine’s protection is perplexing.

It also represents a communications challenge for public health officials who vigorously promote annual vaccination as the most effective way to protect against the flu. Findings that suggest the science is more complicated than initially believed could lead people to assume annual flu shots are detrimental to their health.

That’s not the message researchers such as Belongia want to convey.

“In every scenario, it is better for people to be vaccinated than not vaccinated,” he said. “It would not be, I think, accurate or helpful for people to take away from this ‘Oh, well, I shouldn’t get vaccinated because I got vaccinated in the past and that’s a bad thing.’ ”

Like most issues related to mysterious and mercurial flu viruses, this one is a complex puzzle. But several researchers say the effect appears to be real — and needs to be explored further.

A number of countries are trying to get ever-larger portions of their populations immunized annually against influenza, a fact that makes it all the more important to figure out what is going on, flu experts say.

“The influenza immunization program is our largest, most costly annually repeated immunization program,” said Dr. Danuta Skowronski, an epidemiologist at the British Columbia Centre for Disease Control in Vancouver. “It’s worth it — so worth it — to invest in understanding these effects.”

But getting answers means mounting prospective, randomized clinical trials, and that will be both expensive and complicated.

The work cannot be done in the United States, where the Centers for Disease Control and Prevention has recommended since 2010 that everyone receive annual flu vaccinations. Given that policy, it would be unethical for researchers here to randomly assign some people to forgo vaccinations in some years. But experts elsewhere, including in Hong Kong, where influenza circulates year-round, are trying to put together the funding for what would have to be a large, multiyear study.

The question of the effectiveness of repeated flu vaccines has actually been kicking around for decades. Back in the 1970s a researcher noticed that children at a boarding school who were vaccinated year after year seemed more likely to catch the flu. Later studies disputed the suggestion.

Like most issues related to mysterious and mercurial flu viruses, this one is a complex puzzle.

Then in 1999, a leading influenza researcher, Derek Smith, suggested that in years when a component of the vaccine — say the part that protects against the influenza A family called H3N2 — had changed little or not at all from the previous year’s vaccine, the second year’s vaccine would induce less protection. Smith, now based at Britain’s University of Cambridge, called it negative interference.

The idea is that the antibodies produced in year one may neutralize some of the vaccine in year two’s shot before it can trigger a full immune response, explained Dr. John Treanor, a vaccine expert at the University of Rochester Medical Center in New York.

Smith also argued that when the vaccine viruses were quite different from one year to the next the recipient would actually get enhanced protection. Positive interference, he called it.

Skowronski started to see evidence of negative interference in the mid-2000s, when she and a fellow Canadian researcher, Dr. Gaston De Serres of Quebec’s public health agency, found the flu vaccine was significantly less effective than they had expected. Conventional wisdom at the time was that it cut the risk of catching the flu by 70 percent to 90 percent. But even during flu seasons when the vaccine was well-matched to the viruses making people sick, it wasn’t proving that effective.

In their search for answers, the researchers considered the people they were studying. About 90 percent were getting flu shots every year. “They’re habitual immunizers,” Skowronski said.

Figuring out whether negative interference is real and what can be done about it is important, Treanor said. But if the phenomenon really exists, researchers have unearthed a problem without an immediate solution.

That’s because influenza vaccine protects against three or four different families of flu viruses. The vaccines only come in the combination form.

A number of research teams are working to develop a universal flu vaccine, one that trains the body’s immune system to fight off all flu viruses. The goal is to have a vaccine people might need to take only a few times in their lives, maybe once a decade. That might solve the problem, Treanor said — but he noted a universal flu vaccine could be years away.

In the meantime, high-dose vaccines might help ensure that vaccines don’t become less effective over time. The extra vaccine in the shot might override the dampening effect of previous years’ antibodies. But Treanor cautioned that theory hasn’t yet been put to the test. And the sole high-dose flu vaccine available in the US — made by Sanofi Pasteur — is licensed for use only in adults 65 and older.

Likewise, an adjuvanted vaccine — one that includes a compound that boosts the immune response the vaccine generates — might prove effective. Although none is currently licensed in the United States, one may be coming.

As for changing the frequency with which the flu vaccine is given, it’s far too soon to even contemplate that kind of move, Belongia said.

“The policy of vaccinating every year has been generally successful,” Belongia said. “We wouldn’t want to change that unless we know for sure that we’re changing it to something that’s going to be better. And right now I don’t think we have any good idea what that would be.’’


NATURAL IMMUNITY VERSUS VACCINATION

Contrary to popular belief, natural immunity is not better than immunity from vaccination.

Not all immunity which surfaces from the recovery of natural infections provide long-term protection.

Some natural infections such as pertussis (whooping cough) does not provide long-lasting immunity even after recovering from it.

The immunity wanes after many years, and the person might be susceptible to the infection again.

Routine immunisation provides a point of contact for healthcare at the beginning of life and offers every child the chance of a healthy life from the earliest beginnings and into old age, as vaccines are timed at a particular age to prevent severe complications from an infection.

For example, BCG vaccination against tuberculosis is given at birth, when the baby is most prone to severe complications.

Vaccination is a planned event that is safe and generally well-tolerated, while the outcome of natural immunity from infection is less predictable. For some, the infection may result in severe complications and long-term consequences, including death and organ failure.


Study: Getting flu shot 2 years in a row may lower protection

Mar 1, 2013 (CIDRAP News) – Experts are puzzled by a new study in which influenza vaccination seemed to provide little or no protection against flu in the 2010-11 season—and in which the only participants who seemed to benefit from the vaccine were those who hadn't been vaccinated the season before.

The investigators recruited 328 households in Michigan before the flu season started and followed them through the season. Overall, they found that the infection risk was nearly the same in vaccinated and unvaccinated participants, indicating no significant vaccine-induced protection, according to their report in Clinical Infectious Diseases. That contrasted sharply with several other observational studies that found the vaccine to yield about 60% protection during the same season.

In trying to figure out why the effectiveness was so low, the researchers sifted their data in different ways, said Arnold S. Monto, MD, of the University of Michigan, senior author of the study. "We discovered that if you separated out those that had not been vaccinated the previous year, you got percentages close to what were seen in the major vaccine effectiveness studies," he told CIDRAP News.

"We were playing with this for a long time, and there was clear interaction of sequential vaccination and vaccine effectiveness, looking at it in a strictly statistical way," he added. "We felt it had to be separated out."

The vaccine was found to be 62% effective in those who hadn't been vaccinated the previous year. That was similar to findings in the other observational studies and also to the results of a recent, rigorous meta-analysis of randomized controlled trials. In contrast, those who had been vaccinated 2 years in a row (before both the 2009-10 and 2010-11 seasons) got no significant protection.

An additional finding was that the vaccine did not seem to protect participants who were exposed to flu in their own household, though the numbers in that arm of the study were small.

Researchers from the US Centers for Disease Control and Prevention and the University of Hong Kong collaborated with University of Michigan researchers on the study, with Suzanne E. Ohmit, DrPH, of Michigan as the lead author.

The findings come amid a growing number of studies that raise questions about flu vaccine effectiveness (VE). They include, among others, last week's CDC report that this year's vaccine has worked poorly in elderly people and three recent European studies showing that vaccine-induced immunity in the 2011-12 season waned after 3 to 4 months. Other studies have cast doubt on the long-standing belief that a close match between the vaccine virus strains and circulating strains improves VE.

In an editorial commentary accompanying the Michigan study, John Treanor, MD, and Peter Szilagyi, MD, both of the University of Rochester Medical Center, wrote, "As we are currently struggling through one of the most vigorous influenza seasons in recent memory, the apparent failure of influenza vaccine under optimal conditions seen in this study is indeed troubling."

And Edward Belongia, MD, a Wisconsin clinician-researcher and member of the CDC's Influenza Vaccine Effectiveness Network, said he was perplexed by the low overall VE in the study, given the approximate 60% protection levels found in studies by the network the same season. "I don't know what to make of it," he told CIDRAP News.

Other researchers have said that additional studies suggesting a negative effect of prior-year vaccination on flu VE will be emerging in coming months, but they declined to give any details.

Aiming to detect all cases
The researchers used a prospective cohort design in an effort to detect all flu cases in the study group, regardless of whether or not participants were sick enough to seek medical attention.

The team sought to recruit households that had at least four members with at least two children and that received medical care through the University of Michigan Health System, based in Ann Arbor. Out of a target group of 4,511 households, the authors recruited 328, with 1,441 members.

Participants were instructed to report any acute respiratory illnesses throughout the flu season. Individuals with symptoms went to a study site for collection of a throat swab for flu testing. The researchers followed the illnesses to collect data on disease course, including whether the volunteers sought medical attention. Specimens were tested using polymerase chain reaction (PCR).

Among the 1,441 participants, 866 (60%) had documentation of receiving a flu shot for the 2010-11 season, with coverage lower among younger adults and higher in those with high-risk health conditions. Of those vaccinated, 88% received an inactivated vaccine and 12% the live-attenuated vaccine.

During the season, 624 individuals reported 1,028 acute respiratory illnesses, leading to the collection of 983 specimens. Of those, 130 specimens from 125 participants (13%) were positive for flu. By subtype, 45% were influenza A/H3N2, 34% were type B, and 20% were 2009 H1N1. Thirty-two percent of the cases led to medical attention.

Among the 125 people who tested positive for flu, 59% had been vaccinated at least 14 days before their illness onset, long enough for an immune response. The infection risk in the vaccinated people was 8.5% (74 of 866), versus 8.9% (51 of 575) in the unvaccinated individuals.

Community vs household transmission
The researchers estimated VE separately for community and household exposures. Ninety-seven flu cases were classified as community-acquired and included in the analysis. After adjustments for age and high-risk medical conditions, the all-ages VE was estimated at a nonsignificant 31%, (95% confidence interval [CI], –7% to 55%). VE estimates by age-group were similar and likewise nonsignificant.

The result was very different when the team stratified the participants according to whether they'd had a flu immunization the previous season. As noted above, estimated VE in those with no prior-year immunization was 62% overall (95% CI, 17% to 82%), whereas VE in those who did get vaccinated the year before was low in all age-groups and came out to –45% overall (95% CI, –226% to 35%).

The team defined a household-acquired case as one that occurred within a week after another case of the same subtype in the same household. On this basis they determined that 30 flu cases were household-acquired. The estimated VE for this group was –51% overall (95% CI, –254% to 36%), and the age-group estimates were all low.

"Adults were at particular risk of infection despite vaccination," the report says. "In fact, 9 of 11 (82%) adults with household acquired influenza were vaccinated, compared with 11 of 19 (58%) children." In this group the team found no major differences related to prior-season vaccination.

The authors found that the flu risks were similar for adults who were vaccinated in both years and those who weren't vaccinated in either year. The pattern was slightly different in children under 9 years old, in that those with no vaccination either year had the highest risk of infection.

Summing up, the report notes that VE estimates against community-acquired flu of all severities were all less than 40% and "not statistically different than zero" (because of confidence intervals that overlapped zero). "This unexpected finding was seen in a season with circulation of influenza strains that were considered matched to vaccine strains, and where evaluation of vaccine effectiveness using case-control designs indicated significant reductions of 52 to 60% in medically attended influenza outcomes in vaccinated patients of all ages."

Monto said possible explanations for the low VE within households include that the vaccine may be "overwhelmed" by continual exposure to an infected family member, particularly since children shed more virus than adults.

He said his team is working on further studies of flu VE in the community and households and is collecting blood samples to examine immune responses to vaccination and infection, a step that was not possible in the current study. That may help shed some light on the unexpected findings, he said. For now, "We can only speculate about what's really going on from an immunology standpoint."

Monto commented that the study raises tough questions. "We recommend vaccination every year because we know the duration of protection is relatively short. What are we to do if we know that being vaccinated every year is perhaps not the best way to get good vaccine effectiveness?" he said.

Intriguing and troubling
In the accompanying commentary, Treanor and Szilagyi call the findings "intriguing" as well as troubling. They suggest some factors that may help explain the differences between the current findings and other VE studies, but they make it clear there are no easy answers.

Treanor and Szilagyi contrast the approach used in the Michigan study with the test-negative case-control design, which several large research networks have been using to assess flu VE. In the latter design, patients seeking care for an acute respiratory illness are tested for flu and their vaccination status is determined. The case-control approach has important pluses, but it is "somewhat incomplete" because it is limited to medically attended cases.

In comparison, Ohmit and colleagues were able to assess VE against both medically attended and unattended illnesses, as is true in randomized controlled trials (RCTs), Treanor and Szilagyi write. But the findings in this case were "strikingly different" from those in some recent RCTs and case-control studies of flu VE.

Various undetected biases might help explain the low VE found in the study, Treanor and Szilagyi say. For example, people who choose to be vaccinated may be more health conscious and more likely to report illnesses, compared with those who don't get vaccinated. Also, the households that enrolled in the study—only 7% of the target group—may differ from the general population in some way.

Treanor and Szilagyi say concerns about the possible effect of previous vaccination on VE have been raised before, particularly in a 1979 study of students in British boarding schools. But later randomized trials did not show a consistent effect.

Given the many persistent questions about flu VE, it may be time to rethink the view that randomized trials are unethical, the two commentators suggest. "Given that the effectiveness of the vaccine is unclear, [that] the subjects in such studies are typically at extremely low risk of serious disease, and that effective antiviral therapy is available, perhaps [the ethics] should be reconsidered," they write.

More research needed
Angus Nicoll, MB, director of the influenza program at the European Centre for Disease Prevention and Control in Stockholm, praised the study and said the question of prior-year vaccination clearly needs more investigation.

"Our bottom line is that immunization is the most effective single thing you can do to protect yourself [from flu], and this isn't going to change what we say," Nicoll said. But he added, "It's an important finding, and this does now need to be looked at in the longer term and a larger cohort." He commented that the question calls for study in a stable community where the turnover of residents is not too high.

The study also won praise from Belongia, who has studied flu VE extensively at the Marshfield Clinic Research Foundation in Wisconsin. "I think they did a fine job with the study," he said. "I applaud them for trying to do a community-based study, which is hard to do these days."

He agreed that the finding of an effect of prior-year vaccination is important. "It needs to be looked at in other populations and seasons," he said. "The numbers are relatively small in this study. As the authors note, the majority of people who get the vaccine get it year after year, so there may be important differences between those who get vaccinated repeatedly and those who just recently chose to do it."

As noted above, Belongia was particularly puzzled that the overall adjusted VE in the Ohmit study, at 31%, was only about half what was found in case-control studies the same season. "I think a key message is that we need more community-based studies, with PCR-confirmed outcomes," he said.

Another flu vaccine researcher, Heath Kelly, of the Victoria Infectious Diseases Reference Laboratory in Melbourne, Australia, said the suggestion that prior-year vaccination affects flu VE is not new, pointing to a study of British children in 1979. He noted that another research group developed a model suggesting that this effect is related to the antigenic distance between the current and previous vaccines and the circulating viruses.

Kelly said he found it "intriguing" that the Michigan study failed to find a significant protective effect of vaccination, "given that many observational studies in Europe, Canada, and the US found moderate protection against medically attended, PCR-confirmed influenza in the 2010-11 season."

He remarked that the 62% effectiveness seen in those who were not vaccinated the previous year is similar to other published estimates, mainly from sentinel surveillance programs. "Although it seems unlikely, could it be that the sentinel schemes include a majority of people who were not previously vaccinated?" he asked.

Another flu expert, Michael T. Osteholm, PhD, MPH, said the findings further complicate the already difficult challenge of framing flu vaccination recommendations. Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy, which publishes CIDRAP News, was the lead author of a lengthy 2012 report on the flu vaccine landscape and the need for better vaccines.

"We're at a major crossroads in integrating our current influenza vaccine science with our current flu vaccine recommendations," he said. "The issues of vaccine efficacy by age and by vaccine [formulation] as well as the concept of waning immunity in a given season, the lack of correlation between vaccine virus match with circulating viruses and protection, and the potential for repeated annual vaccination to lower one's protection, versus not being repeatedly vaccinated, are all immense challenges for us today.

"If we don't go back and revisit our current vaccine recommendations, I think we stand to lose a great deal of credibility with both the medical community and even the general public as to the trustworthiness of what public health concludes and promotes," he said. "This is exactly why we need game-changing influenza vaccines."

Ohmit SE, Petrie JG, Malosh RE, et al. Influenza vaccine effectiveness in the community and the household. Clin Infect Dis 2013 Feb 14 (early online publication) [Abstract]

Treanor JJ, Szilagyi P. Influenza vaccine—glass half full or half empty? (Editorial Commentary) Clin Infect Dis 2013 Feb 14 (early online publication)


Why does COVID-19 infection sometimes cause severe illness and death while the vaccine doesn't?

The goal of a virus is to make copies of itself, and it's evolved to mess with its host's innate immune system to facilitate that, by suppressing or "dysregulating" it.

"Unfortunately, with SARS-CoV-2, it seems that in some cases, there is this kind of depression or inhibition of our antiviral response but over-activation of our inflammatory response," Kelvin said. That can result in massive damage to the body's tissues, such as lung tissues, without actually clearing out the virus.

The parts of the virus that dysregulate the immune system are generally not present in vaccines.

In fact, while activating the innate immune system is needed to activate the adaptive immune system, the spike protein alone doesn't do that. That's why compounds called adjuvants, which generate their own "alarm signals" for the innate immune system, are typically added to protein-based vaccines. But vaccine makers try to keep that response to the minimum required.

Prof. Jen Gommerman, Canada Research Chair in Tissue Specific Immunity at the University of Toronto, says the dose of virus or spike protein a person receives is another factor, and may vary a lot in a natural infection.

With vaccines, clinical trials test different doses and settle on the optimal one.

"This dose is calibrated to initiate a good immune response that doesn't make you sick," Gommerman said.

WATCH | Is one vaccine better than the other?

COVID-19: Is one vaccine better than another?


Why flu vaccines don’t protect people for long

The annual influenza vaccine saves lives and spares many people from severe disease, which is why governments and employers promote and subsidize its use. But it’s hardly an ideal vaccine, offering so-so protection that wears off rapidly. A new, one-of-its-kind study, published today in Science , helps explain those shortcomings: A key cell type hidden in bone marrow that quickly kicks into activity after vaccination fades within a few months, researchers found. The discovery could lead to new strategies to increase the vaccine’s durability.

The best vaccines—such as the ones for measles, rubella, and diphtheria—provide almost 100% protection for life. Flu vaccines, however, often don’t exactly match the rapidly evolving influenza virus, so their effectiveness changes each year: In the United States between 2009 and 2019, it ranged from a low of 19% to a high of 60%. And protection wanes quickly: If you live in a temperate region of the world and receive the shot in the early fall, immunity can disappear before the end of that winter.

To better understand the durability problem, Rafi Ahmed, an immunologist at Emory University School of Medicine, homed in on a type of B cell that resides in the bone marrow and whose role Ahmed helped uncover in 1996. B cells make antibodies that can attach to and disable viruses. Ahmed focused on a type of B cell called bone marrow plasma cells (BMPCs), which continuously produce antibodies after an infection or vaccination. So-called memory B cells also produce antibodies and are created the same way, but in contrast to BMPCs, they do not steadily pump out the protective proteins. Instead, as their name implies, memory B cells that are trained to recognize a specific virus kick into gear only when they’re re-exposed to it. It takes them several days after an infection to produce high levels of antibodies—a disadvantage in influenza, which can cause disease rapidly.

To the surprise and disbelief of many, Ahmed’s group showed in 1996 that some BMPCs can live for many years, meaning they could, in theory, confer long-lasting immunity. Whether influenza vaccines trigger high levels of BMPCs and if so, whether the cells are the long-lived variety was a mystery, however.

Ahmed and colleagues repeatedly examined the bone marrow and blood of 53 volunteers aged between 20 and 45 years old in the weeks and months before and after they received influenza vaccines. (Some people participated over more than one flu season.) The study was no fun for the participants: Removing fluid from within a bone is a challenging and painful procedure that involves piercing the pelvic bone with a special needle. “The logistics … were very difficult, and I think nobody will ever try to do the same thing again,” Ahmed says.

Rino Rappuoli, chief scientist at GlaxoSmithKline Vaccines, says he knows of no other study that sampled bone marrow for vaccine research. “Rafi’s work is great and pioneering,” Rappuoli says.

The researchers found spikes of BMPCs specific for influenza 4 weeks after immunization. But after 1 year, the new cells were virtually gone. Rappuoli and others aren’t particularly surprised by this but welcome the evidence. “This finding tracks nicely with the observed rapidly waning [blood] antibody titers and decreasing protection in humans after getting the flu vaccine,” says Adam Wheatley, an immunologist at the University of Melbourne. “It’s a really nice piece of work.”

The study “helps define the landscape” of the flu vaccine’s lousy durability, says Mark Slifka, an immunologist at Oregon National Primate Research Center who earned his Ph.D. with Ahmed more than 20 years ago but was not involved with this work. “They chipped away at the stone in terms of understanding why the immune response is short-lived,” Slifka says.

But Slifka thinks the BMPC population stimulated by vaccines likely has a small proportion of long-lived cells, undetected in this study, that could offer more enduring protection. The way to boost their presence is to goose the system so that it makes more BMPCs overall, he says. One possible way to do this is with adjuvants, additives to vaccines that act as irritants, ramping up the immune response. It also may help to increase the amount of viral proteins in the vaccines, he says.

The first influenza vaccines, developed in the 1940s, used adjuvants. They contained killed flu viruses mixed it with a water-in-oil emulsion called “incomplete Freund’s.” But the adjuvant caused ulcers at the injection site, so it was dropped from later vaccines. To further reduce unwanted reactions, researchers also stopped injecting the entire killed virus, replacing it with only the surface proteins from the virus. The resultant vaccines had fewer viral proteins and no immune-boosting agents. These vaccines, used widely today, cause far fewer side effects—but they came at a steep cost, says Slifka, who last year published a review article that hammered in these points. “We’ve damaged the immunogenicity and the durability of the response.”

But for the past 2 decades, improved adjuvants have found their way into licensed vaccines. A revamped influenza vaccine that has an oil-in-water adjuvant—the water shields the oil and makes it safer—has been used in Italy since 1997 and was approved by European and U.S. regulators in 2000 and 2015, respectively. But whether it’s able to trigger long-lasting BMPCs is unclear. No one in Ahmed’s study received this product—when the project began, it wasn’t even licensed in the United States—which is “a pity,” Rappuoli says.

“It’s totally crazy” that most commonly used influenza vaccines don’t include an adjuvant, Ahmed says. “I’m hoping that things will change in the influenza vaccine world, and 10 years from now, you will not be getting any nonadjuvanted vaccines. This has been going on for years. It’s hard to change the industry.”


Which offers more protection: Vaccination or natural immunity?

Credit: Modern Healthcare

Let’s start by demonstrating the pandemic’s continuing politicization with the Tweets of the Senator from Kentucky.

Perhaps a more interesting question is whether there are advantages or disadvantages to natural versus artificial, i.e., vaccinated immunity?

The short answer is that it makes no difference to our immune system. Whether the antigen is a virus or bacteria, or a snippet of same, made by man, the immune system recognizes it as foreign and “does its thing.” Its thing, of course, is to develop an immune response. That transformation occurs in the bloodstream and lymph nodes irrespective of whether the antigen got in from our nose, mouth, digestive tract, lung, or via a needle.

That said, there are a few differences. Natural immunity requires enough antigen, viral or bacterial, to be identified and cause the immune system to respond. More antigen gives a more robust response. But that response varies several-fold – a mild case involving minimal symptoms may result in more of a half-hearted natural immunization than you would hope for.

Before considering the variability of response, let’s dig into the cost of natural immunity – you have to be infected and may suffer significant consequences. When looking at a lethal disease, like COVID-19, or infection with substantial morbidity, like brain damage from measles or paralysis from polio, the cost can be quite high. Vaccines are far safer than acquiring immunity by becoming ill. That is the tradeoff underlying the fight over letting herd immunity develop naturally. Herd immunity will develop, but there are going to be a lot of deaths along the way.

Credit: AFP

For most immunities, vaccines not only are safer but produce a more robust response. This includes vaccines for HPV, tetanus, and pneumonia mumps is an exception. The other benefit of a vaccine over natural immunity is its standardization. First, unlike acquiring natural immunity, you can choose when you get vaccinated. Second, while natural immunity provokes a range of responses, vaccines are designed to create the most significant immune response without safety concerns.

For the COVID-19 vaccines, there remain two questions. How long will the immunity last? We don’t know yet, but only time will tell. Again, most vaccines confer equally long-lasting immunity. The two mRNA vaccines are targeted at the spike protein. Natural immunity can target the spike and other viral shapes, which might allow natural immunity to protect against some variants again, we do not know. What we do know is that getting your immunity by contracting COVID-19 is a crapshoot being vaccinated is exceedingly efficacious and safe.

“Because vaccines are made using parts of the viruses and bacteria that cause disease, the ingredient that is the active component of the vaccine that induces immunity is natural. However, critics point to other ingredients in vaccines or the route of administration as being unnatural.”

– Immune System and Health Children’s Hospital of Philadelphia

Vaccines include three common ingredients, an adjuvant, a stabilizer, and, often, a preservative. The Pfizer vaccine contains no adjuvant you might think of the first dose priming your immune system for the second although the first confers significant immunity. Instead of a stabilizer, the mRNA is wrapped in a bit of fat with some salts and sugar, called a nanoparticle. It contains no preservatives. Moderna’s vaccine is essentially the same, differing in the elements of the nanoparticle. Johnson & Johnson’s vaccine uses a different delivery method for the antigen. It makes use of an adenovirus –one that causes the common cold and that has been attenuated to cause no symptoms. It is stabilized using a sugar, and the preservative is a citrate commonly found in food.

“I believe that morally everyone must take the vaccine. It is the moral choice because it is about your life but also the lives of others.”

– Pope Francis

Catholics have raised concern about the J&J product because the vaccine’s production involves using a cell line obtained from aborted fetal tissue. The initial statements by local church officials were mixed messages. In 2005 the Vatican’s Pontifical Council of Life indicated that there were “Degrees of Cooperation with Evil” – that the further one was from the act of abortion, the less evil the involvement. The Pope has stated, and now the US Catholic leadership has concurred, that a devout Catholic should choose a different vaccine when given a choice. Still, when there is no choice, the Johnson & Johnson vaccination is “morally acceptable.”

But I will give the last word on the topic to ACSH friend Dr. Paul Offit – the Director of the Vaccine Education Center and professor of pediatrics in the Division of Infectious Diseases at Children’s Hospital of Philadelphia.

Dr. Charles Dinerstein, M.D., MBA, FACS is Senior Medical Fellow at the American Council on Science and Health. He has over 25 years of experience as a vascular surgeon. He completed his MBA with distinction in the George Washington University Healthcare MBA program and has served as a consultant to hospitals. While no longer clinically active, he has had his writing featured at KevinMD and Doximity. Follow him on Twitter @CRDtoday

A version of this article was originally posted at the American Council on Science and Health and has been reposted here with permission. The ACSH can be found on Twitter @ACSHorg

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.


What Getting The Flu Vaccine Every Year Does To Your Immunity

Getting a flu vaccine is like wearing underwear. Just because you did it last year, doesn't mean you shouldn't do it this year.

Also, similar to underwear, the protection offered by a flu vaccine does not last forever. While the duration of protection can vary significantly from person to person, in some cases, the protection may wear off in 6 months or so, which is still much longer than you should wear a pair of underwear. That's one reason why you should get a flu vaccine every year. Assuming that you are 6 months and older because you can read this and you don't have a medical reason (e.g., life threatening allergy) to not get the vaccine.

Another reason is that strains of the flu virus are like reality television stars. Different ones come and go from year to year. Therefore, the strains in a flu vaccine and thus the strains that you end up being protected against vary from year to year.

And if you are worried that getting the flu vaccine every year will somehow reduce your immunity against the flu, look at the study just published in JAMA Network Open. In fact, don't just look at it, read it.

For the study, a research team recruited kids who had visited outpatient clinics at Baylor Scott & White Health (Temple, Texas), the Marshfield Clinic Research Institute (Marshfield, Wisconsin), the Vanderbilt University Medical Center (Nashville, Tennessee), and Wake Forest School of Medicine (Winston-Salem, North Carolina) during the 2013-2014, 2014-2015, and 2015-2016 flu seasons. In order to qualify for the study, a kid had to have a fever and an acute respiratory illness and be real kids (ages 2 to 17 years) instead of just really immature adults.

The research team ended up enrolling 3369 children in the study. Each kid received a flu test. The researchers checked whether each kid had received the flu vaccine the prior year. This allowed the researchers to divide the kids into 4 groups, based on whether they had received the flu vaccine the enrollment year and the year prior:

  • Received the vaccine both the enrollment year and the prior year.
  • Received the vaccine just the enrollment year
  • Received the vaccine only the prior year.
  • Did not receive the vaccine either year

About 23% (or 772) of the kids ended up testing positive for influenza. Around half (or 1674) had received the flu vaccine. The kids could have received one of two different types of flu vaccine each year: the one with the live but weakened virus that is squirted up your nose and the one with the dead virus that is injected into your arm.

The Flumist vaccine is back this year. (Photo by Jeff Gritchen/Digital First Media/Orange County . [+] Register via Getty Images)

The researchers tried to estimate the effectiveness of the flu vaccine by comparing the percentage of people who ended up testing positive for influenza among those who got the vaccine versus those who did not get the vaccine during enrollment year. Of course, this is a somewhat indirect way to estimate the effectiveness of the flu vaccine. Plus, kids visiting a clinic for a fever and respiratory illness do not necessarily represent the general population.

Nonetheless, the study found no evidence that getting the vaccine the prior year reduced the effectiveness of the vaccine the subsequent year. In other words, based on the study results, getting the vaccine last year won't make the vaccine less effective and you more likely to get the flu this year. In fact, the study results suggested that getting the vaccine the prior year may help further boost the vaccine's protection against the certain types of influenza, the B types.

So, why not get the flu vaccine each and every year, as the Centers for Disease Control and Prevention (CDC) recommends? And change your underwear much, much more frequently. If you want to maximize your immunity against the flu, you have to get the vaccine each and every year. There is just no other scientifically proven way to substantially boost your immunity against this virus that could potentially kill you no matter how healthy you may be. Sure, keeping healthy by eating well and staying physically active can help to some degree. But a supplement, a particular food item, or magic potion will not offer you the same immunity against the flu that a vaccine can. Don't listen to those selling supplements who are making claims of protection against the flu that have no real supporting scientific evidence. Like underwear that's been on too long, a lot of the bogus flu protection claims out there can get pretty stinky.


Did seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu?

Did seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu?

In September 2009, news stories reported that researchers in Canada had found an increased risk of pandemic H1N1 (pH1N1) influenza in people who had previously been vaccinated against seasonal influenza. Their research, consisting of four different studies, has now undergone further scientific peer review and is published in the open access journal PLoS Medicine.

Did previous vaccination against seasonal flu increase the risk of getting pH1N1 flu? Based on these studies -- conducted by a large network of investigators across Canada led by Principal Investigator Danuta Skowronski of the British Columbia Centre for Disease Control in Vancouver, in collaboration with provincial leads Gaston De Serres in Quebec, Natasha Crowcroft in Ontario and Jim Dickinson in Alberta -- the answer remains: "possibly."

In a school outbreak of pH1N1 in spring 2009, people with cough and fever were found to have received prior seasonal flu vaccination more often than those without. Several public health agencies in Canada therefore undertook four additional studies during the summer of 2009 to investigate further. Taken together, the four studies included approximately 2,700 people with and without pH1N1.

The first of the studies used an ongoing sentinel monitoring system to assess the frequency of prior vaccination with the 2008-09 seasonal vaccine in people with pH1N1 influenza (cases) compared to people without evidence of infection with an influenza virus (controls). This study confirmed that the seasonal vaccine provided protection against seasonal influenza, but found it to be associated with an increased risk of approximately 68% for pH1N1 disease.

The further 3 studies (which included additional case-control investigations in Ontario and Quebec, as well as a transmission study in 47 Quebec households where pH1N1 influenza had occurred) similarly found between 1.4-2.5 times increased likelihood of pH1N1 illness in people who had received the seasonal vaccine compared to those who had not. Prior seasonal vaccination was not associated with an increase in hospitalization among those who developed pH1N1 illness.

These studies do not show whether there was a true cause-and-effect relationship between seasonal flu vaccination and subsequent pH1N1 illness (as might occur if, for example, the seasonal vaccine modified the immune response to pH1N1), or whether the observed association was not a result of vaccination, but was instead due to differences in some unidentified factor(s) among the groups being studied.

If the findings from these studies are real they raise important questions about the biological interactions between pre-existing and novel pandemic influenza strains. The researchers note, however, that the World Health Organization has recommended that pH1N1 be included in subsequent seasonal vaccine formulations. This will provide direct protection against pH1N1 and thereby obviate any risk that might have been due to the seasonal vaccine in 2009, which did not include pH1N1.

In an accompanying commentary in PLoS Medicine, Lone Simonsen and Cécile Viboud, who were not involved in the studies, write: "Given the uncertainty associated with observational studies, we believe it would be premature to conclude that increased the risk of 2009 pandemic illness, especially in light of six other contemporaneous observational studies in civilian populations that have produced highly conflicting results." They conclude that "this perplexing experience should teach us how to best react to disparate and conflicting studies and prepare us for the next public health crisis, so that we can better manage future alerts for unexpected risk factors."

Funding: This project was funded by the Canadian Institutes of Health Research, the British Columbia Ministry of Health and the British Columbia Centre for Disease Control, Alberta Health and Wellness, the Ontario Agency for Health Protection and Promotion, the Ontario Ministry of Health and Long Term Care, the Ministère de la santé et des services sociaux du Québec, the Institut national de santé publique du Québec and the Fonds de la recherche en santé du Québec (FRSQ). Although agencies of the investigators provided infrastructure in support of the reported studies, the funders did not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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