COVID-19 vaccine boosters: what does the research show?

Janet Sasso , Information Scientist, CAS

Nurse administering booster vaccine

With the announcement of newer mRNA booster recommendations, many are asking whether they or their loved ones should get a COVID-19 booster and what science shows. This blog will explain the basics of boosters, review current expert recommendations, and examine the emerging research that has been published.  

What is a COVID-19 booster shot?

A COVID-19 booster is simply an additional dose of vaccine after an individual is fully vaccinated, with two doses of Pfizer-BioNTech’s or Moderna’s mRNA vaccine or one dose of Johnson & Johnson’s viral vector vaccine and has a typical immune response. Booster vaccines work as their name suggests by boosting the protective effect of the initial vaccine. They stimulate an individual’s immune system to produce additional antibodies and memory B cells and T cells. 

An adult booster vaccine that many individuals are familiar with is the Tdap (diphtheria, tetanus, and acellular pertussis (whooping cough) booster. The Centers for Disease Control (CDC) recommends an adult booster once every 10 years, but special scenarios also encourage the use of boosters. For example, parents and caregivers of infants are encouraged to get a Tdap booster to provide a protective vaccine bubble for vulnerable newborns and infants against the disease whooping cough. A Tdap booster is also encouraged after an injury with potential Clostridium tetani exposure to “boost” the immune system to respond to the bacterial toxins that cause a tetanus infection. 

The COVID-19 booster dose strengthens both the humoral and cellular immunity provided by the initial vaccines, helping the immune system respond more quickly to the SARS-CoV-2 virus when encountered.

Why are COVID-19 vaccine boosters being recommended?  

Especially for certain segments, there is clear evidence that an additional dose for the immunocompromised and a booster for high risk populations would be beneficial. The data below shows that the effectiveness of the COVID-19 vaccines is decreasing with the emergence of variants, waning immunity, and exposure to higher viral loads. The highly transmissible Delta variant became the dominant strain in most areas during summer 2021, changing how vaccine effectiveness looks with the resulting higher case counts. Another aspect to note is that many COVID-19 public health orders such as universal masking ended in the U.S. before or during summer 2021.  

  • CDC researchers show that mRNA vaccines drop from 74.7% effective against infection in March 2021 to 53.1% in July 2021 for nursing home populations.
  • Israeli researchers showed the risk for infection was significantly higher for individuals vaccinated earlier compared to those vaccinated later. Individuals vaccinated in January 2021 had a 2.26-fold increased risk for breakthrough infection compared to individuals receiving vaccinations in April 2021. Like the U.S., Israel vaccinated their most vulnerable populations first, based on age and health status. Therefore, the first vaccinated were at the highest risk for COVID-19 infection. Seventy-eight percent of Israel’s population age 12 and older are vaccinated for COVID-19 with the Pfizer-BioNTech BNT162b2 vaccine.
  • New York researchers also found vaccine effectiveness against infection to decline from 91.7% to 79.8% for all New York adults from May to July 2021, as Delta became dominant.
  • UK researchers analyzed data collected in Britain’s ZOE COVID study. They found that the Pfizer-BioNTech vaccine fell from 88% effective one month after full vaccination to 74% five or six months after full vaccination for the Delta variant. The Oxford-AstraZeneca viral-vector vaccine fell from 77% effective one month after full vaccination to 67% at four or five months after full vaccination.
  • The University of California San Diego Health (UCSDH) researchers saw a sharp decrease in vaccine effectiveness in its healthcare workers from June to July 2021. Vaccine effectiveness exceeded 90% from March through June but fell to 65.5% in July. The Delta variant represented 95% of UCSDH cases by the end of July.

US Vaccine Manufacturer’s Booster Vaccine Administration Recommendations

Vaccine Recommendation
Pfizer-BioTech BNT162b2 Booster dose given 6-12 months after full vaccination
Moderna mRNA-1273 Booster dose given 6 months after full vaccination
Johnson & Johnson COVID-19 vaccine Booster dose given 8 months after full vaccination

Currently Pfizer-BioNTech and Johnson & Johnson (ages 18-64) are recommending the standard dose of their current vaccine, while Moderna is recommending a lowered dose of 50 µg vs. its standard 100 µg dose. Johnson & Johnson is recommending a lower booster dose for individuals 65 years and older.

What does the CDC and FDA say about the COVID-19 vaccine boosters?

There is strong evidence about the need for an additional dose especially within immunocompromised populations who can have a reduced immune response and are more vulnerable to serious illness, hospitalization, and death from COVID-19. While experts agree that a booster would be valuable for at-risk populations, there are differences in government agency recommendations for front-line workers and the general population.  

Agency At Risk Populations* Front-Line Workers General Population
CDC Recommends Recommends Not Recommended
HHS Recommends Recommends Recommends
FDA Recommends Recommends Not Recommended

*Immunocompromised and those over 65.

In mid-August, the Food and Drug Administration (FDA) authorized an additional Pfizer-BioNTech (BNT162b2) or Moderna COVID-19 (mRNA-1273) vaccine dose for immunocompromised individuals. Within a week, the U.S. Department of Health and Human Services (HHS) announced that they recommended COVID-19 booster vaccines for all individuals, pending approval and recommendations from the FDA and the U.S. Centers for Disease Control and Prevention (CDC). The CDC currently recommends a third dose of vaccine for moderately and severely immunocompromised individuals who received the Pfizer-BioNTech or Moderna COVID-19 vaccines to better protect this population. 

However, after the FDA Advisory Committee meeting on September 17, 2021, they concluded that the scientific evidence does not support booster vaccines for the general population at this time; because the current vaccination is still highly effective at preventing severe disease, hospitalization, and death from COVID-19.  Scientifically, the news was positive in that the vaccines are working according to their design, even amongst new variants. However, this FDA Advisory Committee recommendation will be revisited when more scientific evidence supporting widespread boosters is available. 

Most recently on September 22, the FDA officially recommended a Pfizer-BioNTech's COVID-19 booster vaccines to individuals who are 65 and older or at high risk of severe disease and received their second dose at least six months ago. They also specified that health care workers, first responders, and those whose jobs put them at special risk should also be eligible for a booster. This group includes professions such as teachers. 

On September 23 the CDC's Advisory Committee on Immunization Practices(ACIP) voted to recommend a Pfizer-BioNtech Covid-19 vaccine booster to people 65 years or older, long-term care facility residents, and people ages 18 to 64 with underlying medical conditions. However, they voted against offering a booster dose to people 18 to 64 whose occupational or institutional setting put them at high risk for COVID-19 infection such as health care workers, first responders, and teachers.  The committee will revisit this recommendation when more evidence is available.  

Hours later, CDC Director Dr. Rochelle Walensky signed off on her official recommendation for the Pfizer-BioNtech Covid-19 vaccine booster. However, it differed from the advisory committee’s results. Instead, she aligned with the FDA, to include boosters for individuals 18 to 64 whose occupational or institutional setting put them at high risk for COVID-19, citing the best interest of the nation’s public health.

Should the booster be the same vaccine as the first one? 

The CDC currently recommends individuals who received either Pfizer-BioNTech or Moderna’s COVID-19 vaccine series receive the same mRNA vaccine for their third dose. If the mRNA vaccine given for the first two doses is unavailable or is unknown, either mRNA COVID-19 vaccine is appropriate as a booster.

However, there are some early results from the UK, Germany, and Spain that have shown mixing vaccine types produced a higher number of antibodies than those who received two doses of the viral vector vaccine. They used the Oxford-AstraZeneca viral vector vaccine to “prime” the immune system with the first dose and then the Pfizer-BioNTech mRNA vaccine to “boost” with the second dose. Each vaccine type stimulates a different area of the immune system creating a more robust immune response than the viral vector vaccine alone.

The National Institutes of Health (NIH) is currently conducting a Phase 1/2 clinical trial to examine a mixed COVID-19 vaccine schedule to determine the safety and immunogenicity of mixed booster regimens.  

CAS COVID-19 Resources:

While boosters may help individuals evade symptomatic infection, they are in no way a means out of the COVID-19 pandemic. Staying ahead of COVID-19 viral variants with the prevention of large outbreaks through global vaccination, boosters, masks, and social distancing will still be critical to minimizing transmission and continued viral mutations. To stay informed on the latest COVID-19 vaccines, technology, and breakthroughs, visit our COVID-19 Resources page for all of our publications, data sets, and insights.