Do we really need vaccine boosters?

Published July 13, 2021, 12:12 AM

by Dr. Edsel Salvana

It’s still under investigation, but here’s what we know


Dr. Edsel Maurice T. Salvana

One of the most common questions I get asked is, “How long do our vaccines last?” Followed closely by, “When can I get a booster?” and “When can I get a second course of vaccines?”

The answer to the first question is still under investigation. Most phase 3 clinical trials started in the second half of 2020, and one year follow-up data are still being collected as we speak. Follow-up data from the sixth month of the original phase 3 vaccine clinical trials are now being analyzed. What has been released suggests that vaccines are continuing to work well within this follow-up period. In other words, there is evidence that the vaccine protection lasts for at least six months, and most scientists think it will last a year or longer.

A recent publication on antibody levels of naturally infected COVID-19 survivors showed that 84 percent of them still had reasonably high antibody titers after eight months from infection. Vaccine-induced immunity is expected to be more robust than that from natural infection. Therefore, if immunity from natural infection lasts at least eight months, we expect to see a longer duration of protection from vaccination.

No data from boosters yet

There is no conclusive clinical evidence that boosters are needed at this time. Vaccine effectiveness, which is the ability of a vaccine to prevent clinical infection, is the key parameter. This includes prevention of symptomatic (with symptoms and a positive RT PCR) or asymptomatic (as diagnosed by a positive swab in an individual without symptoms, subject to RT PCR limitations) infections. The data that have been collected to determine if booster shots are needed are mostly in vitro (laboratory data), measuring persistence of antibody levels over time. These levels have generally remained robust within the limited observation period. Some patients have shown declining antibody levels over a longer period, but this does not mean the vaccine no longer works. A drop in antibody levels is expected if there is no repeat exposure to the virus since it is not advantageous for the body to keep producing high levels of antibodies without an imminent threat. The body has memory B-cells, a type of immune cell in the blood and bone marrow, which can ramp up antibody production quickly if there is re-exposure. Preliminary data suggest that memory B-cells are produced in sufficient quantities months after vaccination.

It also isn’t clear what level of antibody titer is protective. Some neutralizing antibody tests claim US FDA clearance in order to advertise their accuracy. The original FDA clearance, however, for measuring neutralizing antibody levels was meant to measure antibodies as a result of past infection. This is very different from measuring vaccine effectiveness, especially since different vaccines can induce immunity is different ways. There isn’t good prospective evidence that beyond a certain level, higher neutralizing antibody levels necessarily translate to further decreased risk for developing clinical disease.

Different vaccines use different virus components to elicit immunity. Whole inactivated virus vaccines induce a more diverse immune response, including many kinds of antibodies and T-cells (a type of cell that can hunt down viruses hiding in the body’s cells). They may not provoke as high a level of neutralizing antibody compared to mRNA vaccines and spike protein vaccines since neutralizing antibody tests specifically measure spike protein antibodies. There is also evidence that a more robust T-cell response may decrease antibody levels, and so vaccine responses may not be comparable by just measuring antibody levels. The best measure of effectiveness remains prevention of disease, and this can only be determined by measuring clinical outcomes over time.

Giving boosters without good data on the duration of clinical efficacy of vaccines isn’t advisable. Antibody levels aren’t good enough measures of efficacy, especially because these naturally wax and wane depending on exposure and length of time from last dose. Without this data, giving additional doses of a vaccine will carry the higher risk of side effects without any assurance of better efficacy.

The World Health Organization is already studying the use of boosters, but evidence for or against this proposed practice remains sparse. The latest discussions center on whether booster doses should be considered for the most vulnerable, namely elderly patients, those with comorbid conditions, and immunocompromised patients. The current proposed time frame for giving a booster is after at least one year from completion of the original vaccine course, and maybe yearly after that. There is no compelling evidence to support this proposal, and so this is unlikely to become policy until there is better data. There is currently no recommendation to give boosters to the general population.

Insisting on giving boosters without appropriate scientific support can exacerbate the global vaccine shortage, especially for those who live in resource-limited settings. Some populations have not yet gotten any vaccine doses. Administration of booster doses to those who have already gotten protection when vaccine supplies are so precariously short will lead to worsening inequity.

No data yet to support a second course or booster shots for variants

The emergence of more transmissible and deadlier variants has upended the goal of ending the pandemic before year’s end. Data are still being collected on the various vaccine efficacies against these variants. Most readily available data deal with antibody levels, which are difficult to extrapolate and compare among the different vaccines. What seems to be clear is that a full vaccine course (two doses, except for J&J) is needed to retain very good protection against severe disease for these variants. Some countries with high vaccination rates are experiencing increases in cases, but there isn’t as much hospitalization or death.

Without properly controlled data comparing clinical infection among vaccinated and unvaccinated people, it is very difficult to make conclusions about vaccine protection among variants. What data are gathered will not approximate the certainty of clinical trials, and uncontrolled data are susceptible to bias and misinterpretation.

In the case of Israel, where up to half of the cases are breakthrough infections among fully vaccinated individuals, it is easy to jump to the conclusion that the vaccines aren’t working. When considering the high proportion of vaccinated individuals compared to unvaccinated individuals, however, the infection rate is clearly much higher for unvaccinated individuals since the denominator for unvaccinated individuals is smaller. To illustrate, consider this hypothetical scenario: A country has 10,000 people with a 90 percent vaccination rate. Out of twenty infections, 10 are vaccinated and 10 are unvaccinated. The proportion of infection then becomes 10/9,000 for the vaccinated and 10/1,000 for the unvaccinated. That means that the infection rate for vaccinated individuals is 0.11 percent, while that for unvaccinated is one percent, or a nearly 10-fold reduction in infections for the vaccinated.

In the US, despite thousands of new cases daily, death rates have remained relatively low. Dr. Anthony Fauci of the US National Institutes of Health recently stated that 99.2 percent of recent deaths from COVID-19 in the US are from unvaccinated individuals. There will still be a few deaths among vaccinated individuals for a variety of reasons (comorbid conditions, breakthrough infection etc.) but these are expected to be much fewer than in those who are unvaccinated.

The bottom line is that it is too early to get boosters or start a second vaccine course. There is no compelling clinical evidence that a booster or a second vaccine course will result in better clinical efficacy. Getting boosters or a new course of a different vaccine without better supporting data can result in harm from unforeseen side effects. It will also exacerbate the ongoing global vaccine shortage. Controlled clinical trials looking at precisely these questions are ongoing. Until then, we know that the vaccines will continue to protect against severe disease and will continue to save lives.