Boosters are here! Now what?

Published November 23, 2021, 12:12 AM

by Dr. Edsel Salvana

Which brand should you get?

CLINICAL MATTERS

With the FDA giving the greenlight for the use of boosters among healthcare workers this November, the first legal boosters have already gone into some of the A1 group’s arms, including mine. At the time of this writing, only healthcare workers have been cleared to start receiving boosters. The reason for prioritizing healthcare workers is two-fold: They are the most exposed, and they are the most capable of making sound decisions when it comes to interventions with incomplete data. 

The science supporting booster shots remains weak, since no properly randomized studies have been peer-reviewed and published. What is available are preliminary reports from ongoing clinical studies, observational reports, as well as laboratory data on antibody responses. The last category is particularly difficult to interpret as there is no consensus on whether antibody levels truly correlate with real-life clinical protection from disease.

The use of extra doses of vaccines will naturally result in more side effects. This is more pronounced in heterologous (mixed brand) vaccination as seen in early studies. These are not necessarily deadly or severe but can be harmful. Without better data clearly showing a benefit from boosters, the recommendation from the government experts has been to roll this out on a purely voluntary basis.

Despite the availability of nine kinds of vaccines in the Philippines, the Department of Health made the decision to use only four vaccine platforms as boosters: Astra (viral vector vaccine), Pfizer (mRNA), Moderna (half dose only for boosting, mRNA), and Sinovac (inactivated). The DOH has released a matrix that outlines which vaccine boosters are allowed to be used with what primary series of vaccines.

 

With these caveats in mind, these are my recommendations on which vaccine to pick as a booster. Any of the recommendations of DOH are perfectly reasonable. The following is meant as a general guide based on my reading of the most current literature in my capacity as an infectious diseases physician. It should not be taken as a replacement for individualized assessment and advice as each person’s circumstances are unique.

  1. Boosters have been given the go ahead for healthcare workers (A1) only for now. Guidelines for A2 (seniors) and A3 (with comorbids) are still being formulated. The government does not recommend the use of boosters for any other groups at this time. The United States CDC does not recommend boosters for the general population, but only for the elderly, those who are immunocompromised, those with high risk of severe disease, and for those with occupational exposure. 

  2. Boosting is purely voluntary. Since all vaccines are still under emergency use authorization (EUA), these cannot be used without the vaccinees consent. Latest data shows that all COVID-19 vaccines continue to protect against severe disease beyond six months. The potential benefit for healthcare workers who are frontliners is the decreased risk of clinical disease (usually mild), for which the data remains preliminary. This should be a personal decision, and there is no hard deadline. A booster for a frontliner can be requested any time.

  3. Only those who are at least six months out from their second dose are eligible. For the Janssen vaccine, which is only one dose, a booster may be given in three months. The six month cutoff is based on observations that antibody levels wane over time. It is uncertain, however, whether increasing breakthrough infections are from true waning of immunity or the rise of variants that are more resistant to vaccines. 

  4. From a safety standpoint, homologous (same brand) boosters are more predictable in terms of side effects. In other words, if you got Sinovac, Pfizer, or Moderna, you should go for a third dose of the same vaccine if you are concerned about potential side effects. Moderna booster is half of the regular dose. For immunocompromised A3, a third dose of Moderna is considered part of the primary series and given as a full dose.

  5. If you have a choice, avoid a third dose of the Astra vaccine. The Astra vaccine uses a viral vector which our body recognizes as foreign. This results in the formation of antibodies against the virus carrier. A third dose may not be theoretically as effective since the carrier viruses may be neutralized by preformed antibodies as more doses are given. This is why Gamaleya uses two different adenovirus vectors for its Sputnik V first and second doses, in order to avoid decreasing efficacy. If you got Astra for your first two doses, an mRNA booster preferably Pfizer may be the best choice since this combination has the most data.

  6. If you are a frontline worker who takes care of COVID-19 patients and you got Sinovac, there is some preliminary data that a Pfizer or Astra booster gives increased clinical protection compared to a third dose of Sinovac. The protection against severe disease with any of the boosters is more or less equal. The drawback is that mixing vaccines (heterologous) may cause more and stronger side effects.

  7. For non-frontline healthcare workers who got Sinovac, weigh your options. The main decision point is whether you think the modest added clinical benefit, but equal protection from severe disease, is worth the added risk of reactions with a heterologous vaccine. 

  8. Here are the recommendations for different combinations. These are only valid for the A1 priority group.
  1. Got two doses Sinovac more than six months ago, frontliner, no history of adverse drug reaction (ADR) or allergies to vaccines – Pfizer or Astra booster because these show the best incremental increase in protection. While Moderna is allowed, there are not enough studies to determine whether a half dose or a full dose is the most effective strategy. A third Sinovac dose can also be given but is associated with less protection.

  2. For those who got two doses Sinovac more than six months ago, frontliner or non-frontliner with a history of ADR or allergies to vaccines, a third dose of Sinovac is the least likely to precipitate a reaction.

  3. For those who got two doses Sinovac more than six months ago, not a frontliner, no history of ADR or allergies to vaccines, Sinovac or Pfizer or Astra are all viable options. While Moderna is allowed, there are not enough studies to determine whether a half dose or a full dose is the most effective strategy.

  4. For those who got two doses Pfizer or Moderna more than six months ago, either frontline or non-frontline healthcare worker, use a third dose of the same brand keeping in mind that the Moderna booster is a half dose. A homologous strategy for the mRNA vaccines remains the safest option without compromising efficacy. Giving Astra is allowed but less is known about efficacy or safety.

  5. For fully vaccinated healthcare workers with any other vaccine, non-frontline or frontline, a second dose given after six months (or after three months for single dose Janssen) can use either Pfizer or Moderna (half dose) for any vaccine. Or Astra for non-viral vector vaccines. 

We suggest avoiding the Astra booster for viral vector vaccines (Janssen, Gamaleya, Astra) since these are all adenoviruses and there may cause some cross-reaction in antibodies among the adenovirus carriers resulting in decreased efficacy. This is not a safety issue but an efficacy issue and is for now theoretical.

  1. Some general principles based on known side effects of the different boosters:

If with a history of blood clots, avoid Astra booster.

If with a history of myocarditis or pericarditis, avoid mRNA booster.

If with allergy or ADR to previous vaccines, a Sinovac booster might be safer, but this needs to be discussed with DOH as this is technically an off-label use.

A2 and A3 recommendations are forthcoming, and these may have substantial differences with A1 since these populations may have less than full immunity from the primary series. WHO SAGE interim statements in particular recommend a third dose of Sinovac (homologous strategy) for the elderly over heterologous boosting. Do not take any boosters for now if you are in the general population.

All these recommendations are subject to change as the science trickles in. If you are a healthcare worker and you have a hard time deciding, it might be safer to wait for more data as all vaccines will continue to protect against severe disease beyond six months. In the meantime, increasing population immunity by vaccinating the unvaccinated will prevent more hospitalizations and death compared to forcing the issue with boosters outside the target populations. This is turn will shorten the pandemic for all of us.

 
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