COVID-19 Expectations on the Rollout of the Booster Shots

COVID-19 booster shots play a critical role in protecting against infection, hospitalization, and death related to COVID-19 infection, according to infectious disease experts who participated in a recent Contagion Peer Exchange panel, moderated by Peter Salgo, MD, professor of medicine and anesthesiology, Columbia University Vagelos College of Physicians and Surgeons, New York City, New York. However, the panelists added that achieving herd immunity with vaccination may be difficult with the widespread vaccine hesitancy and lack of access to vaccines in developing countries. The panelists reviewed the importance of COVID-19 booster shots for promoting durable immunity, the benefits of COVID-19 vaccination on the individual and public health levels, and the role of booster shots in protecting against new virus variants.

THE IMPORTANCE OF COVID-19 BOOSTER SHOTS

The purpose of the COVID-19 booster is to potentiate the immune system and provide an additional layer of protection from infection, hospitalization, and death, according to Donald Alcendor, PhD, associate professor of microbiology and immunology at Meharry Medical College and adjunct associate professor of pathology, microbiology, and immunology at Vanderbilt University School of Medicine in Nashville, TN. Salgo said that the public may question if the need for booster shots will ever end, but Angela Rasmussen, PhD, research scientist III at the Vaccine and Infectious Disease Organization in Saskatchewan, Canada, noted that vaccines for many other diseases (such as measles, poliomyelitis, and hepatitis B virus infection) have multiple-shot regimens and that the optimal dosing regimen for the COVID-19 vaccines remains to be seen.

“It’s probably correct that we will get to a point where you’ve been sufficiently boosted, that you have very responsive protective long-term–memory immunity to this virus,” Rasmussen said. “Because these vaccines were expedited to the clinic, we don’t really know what the optimal dosing regimen is, but I think it’s very unlikely that we’re going to be needing COVID-19 boosters every 6 months for the rest of our lives.”

Rasmussen added that although the mRNA technology platform used with SARS-CoV-2 vaccines is unique, the fundamental effects of these vaccines on the immune system are similar to those of vaccines with other technology platforms such as adenovirus vectors.

“They expose your immune system to the antigen, in this case the spike protein from SARS-CoV-2, the same way that a protein subunit vaccine would and the same way that an inactivated virus would,” she said. “I don’t that there’s anything fundamentally different to this technology that would necessitate constant boosters. The data that we do have suggest that there are immune responses to both the mRNA and the adenovirus-vectored vaccines that are compatible with long-term–memory immunity.”

Jeff Goad, PharmD, MPH, associate dean of academic affairs, professor and chair of the Department of Pharmacy Practice at Chapman University School of Pharmacy, in Irvine, CA, added that natural disease has not been shown to lead to long-term immunity and that vaccination will be important to possibly achieve herd immunity.

“What we’re seeing is that the human is just not able to develop a long-lasting response, whether we’re using vaccine or natural disease,” he said. “When you start talking about the role of the booster and how many we may need going forward, a lot of it has to do with how well we do with getting the primary series in and now getting the booster in 6 months later because vaccination to herd immunity is going to be critical moving forward.”

HOW COVID-19 BOOSTER SHOTS AFFECT IMMUNITY

The effectiveness of COVID-19 vaccines should be looked at on both the public health and individual levels, according to Jason Gallagher, PharmD, clinical professor, clinical specialist, infectious diseases, and director of the PGY2 Residency in Infectious Diseases Pharmacy at the Temple University School of Pharmacy, in Philadelphia, PA. He said that although “there’s no doubt” about the benefits of a booster following the initial 2-dose regimen from an individual standpoint, providing countries and individuals with their first vaccine doses is the ideal strategy from the public health standpoint. Additionally, the deployment of the vaccines amid a pandemic to try to change its trajectory is unprecedented, Gallagher noted. “We are learning as we go,” he said.

Alcendor said that the vaccine has “yet to let us down” in accomplishing its primary goals of protecting against severe disease, hospitalizations, and death. However, he noted that he has observed a “tremendous amount” of vaccine hesitancy and resistance in several areas of the country, such as in the rural counties of Tennessee where he lives, that is likely to persist and may eliminate the possibility of achieving herd immunity with vaccination.

“We are also dealing with antivaxxers who are putting out misinformation and helping support conspiracy theories around [ill-founded] ideas about vaccine efficacy and safety,” Alcendor said. “We are getting breakthrough infections, and we are getting the evolution of variants that we don’t know if we can control with existing immunity, so we are in a holding place when it comes to herd immunity.”

Alcendor added that even if a country such as the United States has a high vaccination rate, global vaccination is necessary to ensure widespread protection. He said that the low vaccine availability in developing countries, such as those in Africa, is a critical barrier that needs to be addressed.

“Those countries cannot afford vaccine contracts. Vaccine contracts are paid for before the vaccine is even made,” he said. “You’re looking at rich countries having more than 60% of the vaccine supply. What you need to do is this: You need to bring vaccine manufacturing and distribution local to those communities, and that must be done through public-private partnership with vaccine companies and the governments. The World Health Organization must be involved.”

ARE COVID-19 BOOSTER SHOTS NECESSARY?

The panelists agreed that booster shots are necessary, and Rasmussen added that turning down a booster shot in countries of high vaccine access, such as the United States or Canada, does not increase vaccine access to other countries in need.

“I think that the boosters may be necessary for everybody for long-term immunity,” she said. “Are they necessary now to prevent the severe disease that Donald [Alcendor] was talking about earlier? For a lot of people, probably not. Are these really 3-shot vaccine regimens, at least for the mRNA vaccines, and a 2-dose regimen for the adenovirus-vectored vaccines? I do think that they are. The question really is: At what point do you need to deliver those boosters to make sure that everybody is safe? At what point is it urgently needed? I would argue that in people who are low risk for severe COVID-19, boosters are not urgently needed, even though long term they may be needed for that duration of immunity.”

Alcendor added that the push to provide boosters in the United States was likely prompted by data from Israel showing the occurrence of breakthrough infections and decreases in antibody levels over time, but he noted that the effects of T-cell or cell-mediated immunity on the immune response against COVID-19 infection is often overlooked. According to Alcendor, T cells play a critical role in B cell differentiation and synthesis of antibodies, as well as activation of cytotoxic T cells and improving their ability to kill infected cells.

“We are using antibody levels as a surrogate marker for immunity,” Alcendor said. “We never talk about T-cell or cell-mediated immunity as a clear marker that must be looked at.”

However, Goad countered that higher antibody levels may be important for protection against new variants, such as the Omicron variant, that are likely to continue to develop in countries with limited access to vaccination.

“Without…changing the makeup of the vaccines, we can also overwhelm the virus by a higher antibody titer that we’re getting with the booster,” he said. “There may be some protection here that we’re overlooking, especially with new variants coming out.”

Moderator

Peter Salgo, MD

Professor of Medicine and Anesthesiology

Columbia University Vagelos College of Physicians and Surgeons

New York City, NY

Panelists

Donald Alcendor, PhD

Associate Professor of Microbiology and Immunology, Meharry Medical College

Adjunct Associate Professor of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine

Nashville, TN

Jeff Goad, PharmD, MPH

Associate Dean of Academic Affairs, Professor and Chair of the Department of Pharmacy Practice at Chapman University School of Pharmacy,

Irvine, CA

Jason Gallagher, PharmD

Clinical Professor, Clinical Specialist, Infectious Diseases, and Director of the PGY2 Residency in Infectious Diseases Pharmacy

Temple University School of Pharmacy,

Philadelphia, PA

Angela Rasmussen, PhD

Research scientist III, Vaccine and Infectious Disease Organization

Saskatchewan, Canada