Will we need a COVID-19 vaccine booster?

Coronavirus vaccination record card. Protective mask divided into two parts.Concept of defeating Covid-19. High quality photo

As of May 2021, more than 160 million Americans have received at least one dose of a COVID-19 vaccine. The vaccines are shown to be highly effective in preventing infection in trials and in populations living in real–world conditions (Thompson et al. 2021). We do not yet know how long protection will last but recent studies have shown that the Pfizer and Moderna vaccines are highly effective for at least six months. As the United States moves toward herd immunity and restrictions are lifted, especially for those who are vaccinated, many are wondering if they will need a booster and if so, when.

Background
Vaccines help a person develop immunity by imitating an infection. After vaccination, your immune system develops antibodies against a particular pathogen, such as the SARS CoV-2 virus, and if your body encounters that pathogen then the antibodies fight off the infection. For some vaccines, more than one initial dose is required to produce the largest immune response. This is the case for both the Pfizer and Moderna COVID-19 vaccines, which require two initial doses to produce the best immune response. For some vaccines, immunity begins to wear off over time and a booster dose is needed. Common vaccines that require boosters include the measles-mumps-rubella (MMR) and tetanus, diphtheria, and pertussis (Tdap) vaccines. In the case of influenza, a new vaccine is required each year to target the particular virus strains circulating in a given year. Viruses including influenza and SARS CoV-2 are constantly evolving and new strains forming. There are many variants that have evolved from the emergent 2019 strain of the virus including the UK, South African, Brazilian, and Indian variants. A key question is whether the SARS CoV-2 virus will evolve to evade COVID-19 vaccines and, if so, how quickly? This will be one of the determining factors for whether a booster is necessary for COVID-19.

Are COVID-19 vaccines protective against variants?
In a recent national–level study in Israel, the Pfizer vaccine was found to be highly effective against the UK variant (Haas et al. 2021). In addition, the study found that two doses were shown to significantly increase the efficacy compared with one dose. In another recent study in Qatar, the Pfizer vaccine was also shown to work well against the UK variant (Abu-Raddad et al. 2021). The study found that in Qatar protection against the South African variant was lower than against other strains although effectiveness against severe disease leading to hospitalization or death was still extremely high at over 90% efficacy. New variants around the world have developed mutations that at least partially evade existing vaccines in laboratory settings, so the fear is that they will continue to evolve so that the vaccines are no longer as effective in protecting against COVID-19 in populations around the world.

Developing boosters
Recent studies have shown that six months after the second dose the Pfizer vaccine is 91% effective and the Moderna vaccine is 94% effective (Doria-Rose et al., 2021). This sustained vaccine effectiveness in conjunction with a growing vaccinated population proportion is promising. The effectiveness of these vaccines and others will continue to be monitored as the time since people have been vaccinated increases to determine if the vaccine effect wanes over time. New vaccine trials are underway to measure the effectiveness of a booster of existing vaccines after six months from initial vaccination. For instance, trials have begun to measure the efficacy of a third dose of the Pfizer and Moderna vaccines after six months. It is possible that a third dose after months or years will boost immunity and provide enhanced protection against COVID-19. In addition to boosters of the original vaccine, manufacturers are developing boosters targeting variants. The technology behind the Pfizer and Moderna mRNA vaccines makes it easier to more quickly develop boosters that target new variants of the SARS CoV-2 virus. Moderna recently announced that they have developed boosters that target the South African and Brazilian variants and Pfizer has done the same. Studies have begun to determine the protective efficacy of these boosters against variants.

Will we need boosters and when? A prediction
Each day we learn more about COVID-19, the SARS CoV-2 virus, and COVID-19 vaccines. While the COVID-19 vaccines have been proven highly effective, no vaccine is perfect and there will inevitably be so–called “breakthrough cases” of people who have been vaccinated who test positive for the SARS CoV-2 virus. In the United States there have only been approximately 1,300 breakthrough cases reported out of the millions who have been vaccinated and almost all of the cases have been very mild (CDC 2021). It is important to monitor whether the proportion of breakthrough cases in the vaccinated population increases and whether the proportion of severe cases increases over time.

While it is impossible to know whether boosters will be necessary and when they will be most effectively deployed, until the studies providing evidence about their effectiveness, but there are some clues to help us predict answers to these questions. First, the COVID-19 pandemic is still in full force in much of the world and it will not be eliminated anytime soon. Several new variants have formed, spread, and become dominant in different regions of the world and the virus will continue to evolve and new variants will surely form. While the vaccines are still highly effective against all variants, there are slight differences in observed effectiveness that could mean that the virus will evolve to evade the vaccine in the future.

I predict that we will eventually need a COVID-19 booster. It is impossible to know when a booster will be needed until we have more evidence but there are also some clues that can help us predict the answer to this question. The COVID-19 vaccines have, so far, proven to be highly effective and the effectiveness lasts for at least six months. Since the vaccines are still working extremely well in the real world, I predict that boosters will not be necessary for at least a year after full vaccination. It is possible that we will need a COVID-19 vaccination periodically, perhaps every year like the influenza vaccine or perhaps after several years.  Prevention will continue to be our best tool against this virus into the future and COVID-19 vaccines are our most important weapon.

written by Dr. Michael E. Emch

References
Abu-Raddad LJ, Chemaitelly H, Butt AA; National Study Group for COVID-19 Vaccination. 2021. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. N Engl J Med. doi: 10.1056/NEJMc2104974.

CDC 2021.  COVID-19 Vaccine Breakthrough Case Investigation and Reporting. United States Centers for Disease Control and Prevention.  www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html.

Doria-Rose N, Suthar MS, Makowski M, O’Connell S, McDermott AB, Flach B, Ledgerwood JE, Mascola JR, Graham BS, Lin BC, O’Dell S, Schmidt SD, Widge AT, Edara VV, Anderson EJ, Lai L, Floyd K, Rouphael NG, Zarnitsyna V, Roberts PC, Makhene M, Buchanan W, Luke CJ, Beigel JH, Jackson LA, Neuzil KM, Bennett H, Leav B, Albert J, Kunwar P; mRNA-1273 Study Group. 2021. Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N Engl J Med. doi: 10.1056/NEJMc2103916.

Haas EJ, Angulo FJ, McLaughlin JM, Anis E, Singer SR, Khan F, Brooks N, Smaja M, Mircus G, Pan K, Southern J, Swerdlow DL, Jodar L, Levy Y, Alroy-Preis S. 2021. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet. 397(10287): 1819-1829.

Thompson MG, Burgess JL, Naleway AL, Tyner HL, Yoon SK, Meece J, Olsho LEW, Caban-Martinez AJ, Fowlkes A, Lutrick K, Kuntz JL, Dunnigan K, Odean MJ, Hegmann KT, Stefanski E, Edwards LJ, Schaefer-Solle N, Grant L, Ellingson K, Groom HC, Zunie T, Thiese MS, Ivacic L, Wesley MG, Lamberte JM, Sun X, Smith ME, Phillips AL, Groover KD, Yoo YM, Gerald J, Brown RT, Herring MK, Joseph G, Beitel S, Morrill TC, Mak J, Rivers P, Harris KM, Hunt DR, Arvay ML, Kutty P, Fry AM, Gaglani M. 2021. Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers – Eight U.S. Locations, December 2020-March 2021. MMWR Morb Mortal Wkly Rep. 70(13):495-500.

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