Boosters, third doses, and who needs them – Manila Newsletter


Clinical questions

Nothing is more controversial these days than the discussion surrounding extra doses of COVID-19 vaccines. Israel, having achieved a high level of immunization for its citizens, began offering boosters to its elderly population early on, followed by increasingly younger age groups.

The United States then went ahead and initially offered supplemental doses to people who were immunocompromised, especially those who were immunocompromised to levels equivalent to those in solid organ transplant recipients. In layman’s language, this means that your immune system would have to be very weak to qualify.

A few weeks later, the vaccine qualification criteria for the boosters were changed to include those over 65. In a controversial decision in which the Centers for Disease Control and Prevention (CDC) went against the recommendation of its own advisory board, the Advisory Committee on Immunization Practices (ACIP), the CDC recommended that recalls are also offered to people who were at high occupational risk. This disparity of opinion is a clear indication that the science behind boosters and third doses is far from settled.

To make matters even more complicated, many have been baffled by recent reports that the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization (SAGE) recommended a third dose of Sinovac or from Sinopharm for immunocompromised and elderly vaccines. As of this writing, there is no final statement from SAGE, as these recommendations are expected to be formalized in November.

The WHO clarified that the SAGE interim report concerned the third doses of the COVID-19 vaccine, and not the boosters. WHO further said the science of boosters remained inconclusive and it was not clear whether homologous (same vaccine) or heterologous (different vaccine) boosters were equivalent, or whether one was better than l. ‘other. It was also not specific to Chinese vaccines, but all current vaccines could benefit from a third dose for some populations. Unless you are imbued with the science of vaccinology, these statements may seem like a hairstyle. Under these terminological differences lie very important principles in immunology and equity in health care.

When is it considered a third dose, and not a booster?

A third dose in a series of primary vaccines recognizes that two doses of a vaccine may not reliably induce lasting immunity in recipients. For example, a primary series of hepatitis B consists of doses at zero, one and six months. Boosters may be given later for certain populations or occupations, but are not necessary for the general population.

As more and more data emerge for COVID-19 vaccines, some populations, namely the immunocompromised and people over 60 years of age, are less likely to achieve the same efficacy for two doses of COVID-19 vaccine per relative to the general population. Therefore, the interim reporting is to consider a third dose (not a booster) as part of the primary immunization series. The timing of the third dose is still uncertain, but in the future it could be given as early as 28 days from the second dose. A third dose will most likely be of the same (homologous) vaccine.

For the general population, it seems clear that two doses still continue to reliably protect against COVID-19. That may change as long-term data emerge, but the WHO, SAGE, CDC, and US FDA are not currently recommending a third dose for the general population. Therefore, administering an additional dose to this population would be considered a booster and not a third dose.

Who needs a booster?

The strengthening of populations at occupational risk such as health workers is very controversial and very difficult to implement from a political point of view. While all COVID-19 vaccines reliably protect against serious illness for the general population beyond six months, there has been a marked decrease in clinical efficacy, i.e. prevention of symptomatic diseases. It is believed that a booster can raise antibodies enough to restore protection against clinical disease, especially among healthcare professionals, as they cannot afford to get even mildly ill and potentially infect their patients. While there is good data indicating that homologous and heterologous boosters increase antibody levels, it is not clear whether these higher antibody levels add protection against the variants of concern. There is a need for better booster studies, as the benefit in terms of better clinical protection is unclear compared to the risk of additional side effects and depriving unvaccinated populations of rare vaccines.

Recent data from Israel seems to suggest that strengthening may indeed increase both clinical protection and disease severity. However, much of the data collected is within weeks of the booster dose and may be confused by the coincidental increase in Delta cases. Another recent randomized clinical trial with a third dose of Pfizer showed a decrease in clinical disease in those who received a booster compared to placebo, but the data indicating whether there were any differences in the severity of the disease, hospitalization or death have not been published. The average time from the second to the third dose in this trial was 11 months. It is this clinical outcome data that is under scrutiny, as many public health experts and scientists are not convinced that the data reflects a clear booster dose benefit. Nonetheless, the US FDA has recommended recalls for people 18 years of age and older who are at work risk or are at high risk of COVID-19. This will be difficult to implement because these criteria are not as clear as the age or the presence of specific comorbidities. In addition, the US FDA has stated that the mixture of vaccines, at least those available in the United States (Janssen, Pfizer, Moderna) would be acceptable. The CDC and ACIP at the time of this writing have yet to weigh in on the vaccine mix, but are expected to offer guidance on who will be specifically qualified at the right time.

Fairness of a third dose and boosters in areas of shortage

While there are no vaccine supply issues for Israel, the United States, and Western Europe, the rest of the world continues to struggle to provide an adequate amount of COVID-19 vaccines to the general population. Add third doses, boosters and the next childhood immunization and these policies are sure to exacerbate the global vaccine shortage. The WHO has called for a moratorium on recalls at least until the end of the year, but this call is unlikely to be followed by many countries anxious to start increasing their populations.

A third dose for elderly and immunocompromised populations does not raise issues of equity because if the primary vaccination consists of three doses for them, then they are not considered to be fully vaccinated until they have received the third dose. This justifies diverting a third dose from lower priority groups. Reinforcement, on the other hand, raises equity issues, as there is not yet sufficient evidence of additional protection for the target population. The scaling-up will divert vaccine supplies from the low-priority unvaccinated groups, who would clearly benefit from protection with a primary series.

When SAGE releases its final recommendation in November, it will likely recommend a third dose (second dose for Janssen) of the same vaccine for people 60 years of age and older as well as for immunocompromised populations. It’s unclear whether he will recommend boosters given WHO’s statements on fairness. Unless more robust supporting data is available, it is unlikely to recommend boosters for the general population. It is unclear whether the vaccine mix is ​​also recommended, as the data the US FDA is currently reviewing has not yet been made public. There are many studies underway that could provide better information in the coming weeks. Emergency Use Authorizations or EUAs will also need to be updated when these recommendations arrive. In the meantime, please do not mix or get a third dose or a booster until there is a firm recommendation. It is still not certain whether they are safe or effective, and you can deny someone access to a vaccine that could save their life.



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