Covid-19 Boosters – Where From Here?

On December 10, 2020, Pfizer presented to the Food and Drug Administration (FDA) the results of a prospective two-dose placebo-controlled trial in 36,000 people of its Covid-19 messenger RNA (mRNA) vaccine, BNT162b2.1 The vaccine was 95% effective in preventing serious illness in all age groups, regardless of coexisting conditions or racial or ethnic background. A remarkable result. Six months later, studies showed that the protection against serious diseases was maintained.2 The results of these epidemiological studies were consistent with those of immunological studies showing high and long-lived frequencies of Covid-19-specific memory B and T cells, which provide protection against serious disease.3

In September 2021, 10 months after the BNT162b2 vaccine became available, Israeli researchers found that protection against severe disease in people aged 60 or over was enhanced by a third dose.4 In response, the Centers for Disease Control and Prevention (CDC) recommended that people age 65 or older receive three doses of an mRNA vaccine.

In a study published today in the Log,5 Israeli researchers found that in a study population with a median age of 72 years, protection against severe disease was further enhanced by a fourth dose of mRNA vaccine during the wave of infections caused by the B.1.1.529 variant. (omicron) of SARS-CoV-2. These results were considered by the FDA and CDC in their decision-making process regarding the use of an additional booster dose of mRNA vaccine for people age 50 or older.

What about booster doses for younger people? A year after the BNT162b2 vaccine became available, studies in the United States showed that a third dose of the vaccine also boosted protection against serious disease in people as young as 18 years old.6.7 Unfortunately, these studies did not stratify patients by whether or not they had coexisting conditions. Therefore, it was unclear who among these younger age groups benefited the most from an extra dose. Nonetheless, the CDC later recommended that anyone 12 years of age or older should receive three doses of BNT162b2, whether or not risk factors were present. This universal booster recommendation has led some summer camps, high schools, universities, hospitals, and businesses to require three doses of the mRNA vaccine. In February 2022, in a study that did not support the booster recommendation for children, CDC researchers found that two doses of BNT162b2 induced long-term protection against serious disease in children 12 to 18 years old.8

In addition to protection against severe disease, the initial Phase 3 trial of BNT162b2 – which was conducted over a period of several months – also showed 95% protection against mild disease.1 Unlike protection against severe disease, however, protection against mild disease, which is mediated by high titers of virus-specific neutralizing antibodies at the time of exposure, declined after 6 months, as might have been expected. wait there.2 In response, Pfizer studies were published in which a booster dose was shown to restore protection against mild illnesses.9; unfortunately, this protection did not last more than a few months.6 Short-term protection against mild disease will limit the ability of booster doses to reduce transmission.

People are now confused about what it means to be fully vaccinated. It is easy to understand how this could have happened. Arguably the most disappointing error in the use of Covid-19 vaccines has been the labeling of mild illnesses or asymptomatic infections after vaccination as “breakthroughs”. As with all mucosal vaccines, the goal is to protect against serious disease – to keep people out of the hospital, intensive care unit and morgue. The term ‘breakthrough’, which implies failure, has created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus. If we are to go from pandemic to endemic, at some point we will have to accept that vaccination or natural infection or a combination of the two will not provide long-term protection against mild disease.

Also, since recalls are not without risk, we need to clarify which groups benefit the most. For example, boys and men aged 16 to 29 are at increased risk of myocarditis caused by mRNA vaccines.ten And all age groups are at risk for the theoretical problem of “original antigenic sin” – a reduced ability to respond to a new immunogen because the immune system has locked onto the original immunogen. An example of this phenomenon can be found in a study in non-human primates showing that boosting with an omicron-specific variant did not result in higher titers of omicron-specific neutralizing antibodies than boosting with the ancestral strain.11 This potential issue could limit our ability to respond to a new variant.

It is now up to the CDC to determine who benefits most from the booster dose and to educate the public about the limitations of mucosal vaccines. Otherwise, a zero-tolerance strategy for mild or asymptomatic infections, which can only be implemented with frequent booster doses, will continue to mislead the public about what Covid-19 vaccines can and cannot. not to do.

Leave a Comment

Your email address will not be published.