To boost or not to boost—an immunological question

NOVEMBER 9, 2021 — Editor’s note: This op-ed by Bernard Arulanandam, immunologist in the Department of Molecular Microbiology and Immunology and vice president for research, economic development, and knowledge enterprise; and Neal Guentzel, microbiologist in the Department of Molecular Microbiology and Immunology; originally appeared in the San Antonio Express-News.

As long as SARS-CoV-2 continues to circulate—and individuals refuse to immunize themselves to prevent transmission and the onset of new coronavirus variants—additional shots, whether they be called part of a vaccine series or boosters will likely be required, particularly for those who are most vulnerable.

The ongoing debate about COVID-19 vaccine boosters centers on adaptive or acquired immunity, which includes the body’s specific learned responses against disease agents.

The waning of the antibody responses to current COVID vaccines suggests diminished protective immunity against the SARS-CoV-2 virus without a booster shot.

Immunologist Bernard Arulanandam and microbiologist Neal Guentzel of UTSA penned this op-ed for the San Antonio Express-News.

Given this reality and the global interconnectedness that impacts us all, our nation’s medical community is considering several questions:

• Should anticipated U.S. booster doses instead be distributed to other countries to help increase global vaccination rates using possible boosters to vaccinate the unvaccinated, since more than 85% of vaccine doses have gone to high- and middle-income countries, leading to a vaccine inequality with low-income countries having very low vaccination rates?
  
  
• Is the current two-dose regimen of the mRNA vaccines enough since the vaccines continue to offer protection against severe disease and death, or should it be a three-dose series, as with many other vaccines, with that third (or booster) vaccine dose added to re-establish prevention of infection and longer-lived protection that would better control variants until greater numbers of the unvaccinated population can be immunized?
  
  
• Should those who have survived COVID-19 receive a booster as break-through infections have occurred with both vaccine and infection-induced immunity, and a remarkable enhancement of the immune response termed “hybrid immunity” has been observed in those previously infected and given a single dose of mRNA vaccine?
  
  
• Can boosters following the two or three-dose vaccine schedule be custom-designed using new technology to better enhance immunological effectiveness and memory against future unknown variants?

Many vaccines, like those for COVID-19, work through B-cells by creating a comprehensive system of antibodies that protect the body from disease agents like viruses and frequently their variant forms. These “neutralizing” antibodies prevent disease-causing microbes and their toxic products from binding, as through the spike protein on SARS-CoV-2, the virus that causes COVID-19, to receptors on the body’s target cells. These vaccines also produce longer lived protective “memory” B-cells that learn and mature through a series of random and beneficial mutations.

Over time, however, and particularly with increasing age and other immune-compromising circumstances, the body’s response to a vaccine decreases and an added dose of a vaccine is necessary to boost the immune system. This booster strengthens the body’s ability to continue to fight off infections.

Getting a scheduled vaccine series that includes boosters is already a well-documented regimen globally to fight a variety of infectious diseases. Hepatitis B vaccine, for example, is currently administered to newborns at birth. Two subsequent doses are administered at ages 1 to 2 months of age, and 6 to 18 months. This vaccination regimen creates significant long-term immunity against the Hepatitis B virus and ensuing liver disease.

Research clearly shows that one dose of the measles vaccine isn’t enough to protect against this disease. Lifelong immunity against measles is conferred only after a two-dose regimen. Long-term immunity, the kind needed for the best possible protection against diseases, requires the continued presence of protective antibodies through long-lived memory B-cells. Scientists call this maintenance of immunological memory.

The current debate over the COVID vaccine booster further fuels the need for additional research insights to identify new markers that better predict vaccine durability.