COVID-19 Boosters Need to be Encouraged

The topic of boosters is at the forefront of public discussion. Some who are against vaccines have spun booster approval into an indictment against COVID-19 vaccines. In reality, they are all but expected. On the front end of vaccine authorization back in November 2020, data were available for vaccine efficacy and safety. However, no one knew how long immunity would last, but based on dosage schedules of other vaccines, it is highly unlikely that mRNA vaccines would be 2 doses within a month and done.¹ For example, hepatitis B has a 3-dose regime, which is given over 6 to 18 months; diphtheria, tetanus, and pertussis has a 5-dose protocol given over 4 to 6 years; polio has a 4-dose protocol over 4 to 6 years; and measles has a 2-dose protocol over 4 to 6 years.

The dosage given and the timing between dosages are crucial. The use of a 3-to-4-week interval between the first and second doses of the mRNA vaccines was primarily driven to quickly achieve maximum immunity. It was not designed for durability. One dosage of the vaccine was effective against the wild type of virus but not against the United States.²

Kevin Kavanagh, MD

Initial estimates of vaccine durability varied widely, but the hopes were that the Pfizer/BioNTech vaccine would last between 6 months and 2 years. As reported by Infection Control Today® on July 29, 2021, after 5 to 6 months post vaccination, waning immunity was detected, with only a 16% efficacy in preventing symptomatic infections. In the prevention of hospitalizations and severe COVID-19 (along with deaths), the Pfizer/BioNTech vaccine was 82% to 86% effective, respectively.³ However, in the cohort above the age of 60, reinfections were much more dangerous, with 8.6% resulting in hospitalizations and 2% in death.4

Booster Recommendations

The need for boosters was clear, but instead of taking decisive firm action on the Israeli data, the United States governmental committees fumbled the ball and seemed to repeatedly change directions, but then partially recovered by recommending boosters for individuals 65 years of age and older along with those of high risk for infection or occupational exposure.^5-7

Data also indicated that the effectiveness in the prevention of Delta variant infections with the Moderna vaccine was greater than with the Pfizer/BioNTech vaccine (76% vs 42%, respectively).⁸ There are 2 major differences between these mRNA vaccines: Moderna uses over 3 times as much mRNA in the vaccine as Pfizer/BioNTech, and Moderna uses a dosing schedule of 4 weeks between the first and second dose, as Pfizer/BioNTech uses a 3-week interval.

In October, the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) approved boosters for the Moderna vaccine after 6 months with similar guidance as that given for the Pfizer/BioNTech vaccine.⁹ The Johnson & Johnson vaccine, which was previously a single-dose vaccine with 72% efficacy in preventing symptomatic infections,¹⁰ has been authorized for a booster for everyone after 2 months. This should not be viewed as a booster but as part of the standard Johnson & Johnson vaccination schedule. Many are asking, “Why was the Johnson & Johnson vaccine not authorized as a 2-dose vaccine from the start?” The answer is that a greater than 70% efficacy would be considered a well-performing vaccine if immunity did not wane, and most of the population would have become vaccinated and afforded added community protection. However, in August, data from the Veterans Health Administration found that vaccine efficacy in preventing infections dropped to 3% compared with 64% for Moderna and 50% for Pfizer/BioNTech.¹¹

On the near horizon, FDA authorization for the Pfizer/BioNTech vaccine for children 5 to 11 years old is expected. The vaccine dosage is just a third of the adult dose.¹² Although there may be significant pushback regarding immunizations in children, the CDC recommends over 30 vaccine doses for a variety of pathogens, most of these doses are scheduled to be given below the age of 2 years.¹

Who Should Get a Booster?

The disagreement over who should get a booster is not one of interpreting science, but one over the goals of giving boosters. As with most other infectious diseases, many feel the goal should be the prevention of disease and spread of disease, not just hospitalizations and deaths. The term mild COVID-19 is an oxymoron. The devastating long-term effects of COVID-19, along with future emergence of cardiovascular disease in those with minimal initial symptoms, remind us that all SARS-CoV-2 infections may pose grave dangers to those who contract the virus. As stated by Scott Gottlieb, MD, former FDA commissioner: “[T]he administration sent a signal to the pharmacy that they wanted this to be a frictionless process, so I think they want these to be generally available for people who deem themselves to be at sufficient risk of contracting COVID-19 or spreading COVID-19….”¹³

Natural Immunity

Data regarding natural immunity have consistently shown a benefit from vaccination. Francis Collins, MD, PhD, director of the National Institutes of Health, presented data in February 2021, which showed that in those who have been previously infected, a single dose of an mRNA vaccine resulted in a 10- to 20-fold increase in antibody response compared with those who had never been infected.¹⁴ After a second dose, the difference was 10 times greater. There have also been 2 clinical studies that have demonstrated a lower incidence of reinfection in previously infected individuals who have become fully vaccinated.^15,16 The exact dosage recommendations and whether a booster plus vaccination is indicated in those who have had previous infections have not been determined. It needs to be remembered that antibody tests are not a reliable way of determining immunity. “The protective antibodies and their thresholds still haven’t been fully worked out” and “all antibodies bind [to the virus] but only some neutralize.”¹⁷ In addition, varying degrees of infection can produce varying degrees in immune responses. Ibarrondo, et al called “for caution regarding antibody-based ‘immunity passports,’ herd immunity, and perhaps vaccine durability.”¹⁸

Mixing and Matching

The FDA has authorized the mixing and matching of boosters.¹⁹ Mixing and matching may be beneficial to those who have received the Johnson & Johnson vaccination. It was observed that if an mRNA booster is given after a Johnson & Johnson vaccination, immunity is augmented 76-fold as opposed to 4-fold if a Johnson & Johnson booster is given.²⁰ An analogous mix and match benefit has been reported with the AstraZeneca vaccine in combination with a Pfizer/BioNTech booster.²¹

Boosters are of utmost importance not only to protect an individual from reinfections but also to prevent individuals from developing low antibody levels, which may permit viral replication and, through immunological pressure, foster immune-resistant variants. How long the immunity will last after a booster is unknown, but there are signs that it may be more durable because an increased percentage of individuals who received a booster developed swollen lymph nodes.²² We must encourage and administer boosters, but it is also of utmost importance that we decisively counter the movement against vaccinations in the United States and increase the primary vaccination rates in our country.

References

1. Recommended child and adolescent immunization schedule for ages 18 years or younger, United States, 2021. Centers for Disease Control and Prevention. Updated February 12, 2021. Accessed October 24, 2021. https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html
2. Skowronski DM, Setayeshgar S, Zou M, et al. Single-dose mRNA vaccine effectiveness against SARS-CoV-2, including Alpha and Gamma variants: a test-negative design in adults 70 years and older in British Columbia, Canada. Clin Infect Dis. 2021;ciab616. doi:10.1093/cid/ciab616
3. Kavanagh K. Israel to offer COVID-19 booster shots to older citizens. Infection Control Today®. July 29, 2021. Accessed October 24, 2021. https://www.infectioncontroltoday.com/view/latest-data-point-to-a-need-for-covid-19-booster-shots
4. Kavanagh K. COVID-19 booster shots for older Americans might be needed. Infection Control Today®. August 2, 2021. Accessed October 22, 2021. https://www.infectioncontroltoday.com/view/covid-19-booster-shots-for-older-americans-might-be-needed
5. Kavanagh K. Viewpoint: on COVID boosters, CDC panel must recover ball that FDA panel fumbled. Infection Control Today®. September 20, 2021. Accessed October 21, 2021. https://www.infectioncontroltoday.com/view/viewpoint-on-covid-boosters-cdc-panel-must-recover-ball-that-fda-panel-fumbled
6. Kavanagh K. Viewpoint: politics, bad science taints decisions about COVID-19. Infection Control Today®. September 24, 2021. Accessed October 22, 2021. https://www.infectioncontroltoday.com/view/viewpoint-politics-bad-science-taints-decisions-about-covid-19
7. Diamond F. CDC chief vetoes advisors: health care workers can get booster shots.Infection Control Today®. September 24, 2021. Accessed October 22, 2021. https://www.infectioncontroltoday.com/view/cdc-chief-vetoes-advisors-health-care-workers-can-get-booster-shots
8. Puranik A, Lenehan PJ, Silvert E, et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv. 2021;2021.08.06.21261707. doi:10.1101/2021.08.06.21261707
9. CDC expands eligibility for COVID-19 booster shots. Centers for Disease Control and Prevention. October 21, 2021. Accessed October 23, 2021. https://www.cdc.gov/media/releases/2021/p1021-covid-booster.html
10. Bai N. How effective is the Johnson & Johnson COVID-19 vaccine? Here’s what you should know. University of California San Francisco. Updated May 7, 2021. Accessed October 20, 2021. https://www.ucsf.edu/news/2021/03/420071/how-effective-johnson-johnson-covid-19-vaccine-heres-what-you-should-know
11. Cohn BA, Cirillo PM, Murphy CC, et al. Breakthrough SARS-CoV-2 infections in 620,000 U.S. veterans, February 1, 2021 to August 13, 2021. medRxiv. October 14, 2021. Accessed October 21, 2021. https://www.medrxiv.org/content/10.1101/2021.10.13.21264966v1
12. Pfizer and BioNTech announce positive topline results from pivotal trial of COVID-19 vaccine in children 5 to 11 years. News release. Pfizer; September 20, 2021. Accessed October 20, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-positive-topline-results
13. Gottlieb S. Transcript: Dr. Scott Gottlieb on “Face the Nation”, October 24, 2021. CBS News. October 24, 2021. https://www.cbsnews.com/news/transcript-dr-scott-gottlieb-on-face-the-nation-october-24-2021/
14. Collins F. Is one vaccine dose enough after COVID-19 infection? NIH Director’s Blog. February 23, 2021. Accessed October 19, 2021. https://directorsblog.nih.gov/tag/covid-19-reinfection/
15. Cavanaugh AM, Spicer KB, Thoroughman D, et al. Reduced risk of reinfection with SARS-CoV-2 after COVID-19 vaccination — Kentucky, May–June 2021. Centers for Disease Control and Prevention. August 13, 2021. Accessed October 17, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm
16. Gazit S, Shlezinger R, Perez G, et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. medRxiv. August 25, 2021. Accessed October 17, 2021. https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1
17. Abbasi J. The flawed science of antibody testing for SARS-CoV-2 immunity. JAMA. 2021;10.1001/jama.2021.18919. doi:10.1001/jama.2021.18919
18. Ibarrondo FJ, Fulcher JA, Goodman-Meza D, et al. Rapid decay of anti–SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med. 2020;383(11):1085-1087. doi:10.1056/NEJMc2025179
19. Coronavirus (COVID-19) update: FDA takes additional actions on the use of a booster dose for COVID-19 vaccines. News release. FDA; October 20, 2021. Accessed October 23, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-additional-actions-use-booster-dose-covid-19-vaccines
20. Zimmer C. Mix-and-Match Covid boosters: why they just might work. The New York Times. October 20, 2021. Accessed October 23, 2021. https://www.nytimes.com/2021/10/19/health/covid-vaccine-mix-match.html
21. Jesús Rodríguez-Baño. COVID-19: lessons learned in Spain. Health Watch USA YouTube page. https://youtu.be/pWuu10Gg7ro
22. FDA authorizes booster dose of Pfizer-BioNTech COVID-19 vaccine for certain populations. News release. FDA; September 22, 2021. https://www.fda.gov/news-events/press-announcements/fda-authorizes-booster-dose-pfizer-biontech-covid-19-vaccine-certain-populations