COVID-19 Vaccines Work Better and for Longer Than Expected Across Populations, Including Immunocompromised Individuals

Monica Gandhi, MD, MPH


May 27, 2022

The mRNA vaccines are powerful in terms of preventing severe disease with COVID-19 across populations because of the multifaceted immune response they generate, a redundancy that can help among patients on agents which cause immunocompromise. Although antibodies from the vaccines will wane over time, or these antibodies can be less effective against new variants like Omicron, the vaccines do not just produce antibodies. The vaccines also generate something called cellular immunity, which is much longer lasting and protect against severe disease in a more enduring fashion.

B-cells and T-cells

Antibody-producing memory B-cells — generated by the vaccines or as a result of a prior infection — have been shown to recognize the virus, including the ability to adapt to the variant to which they are exposed. Although we do not know how long these memory B cells last, survivors of the 1918 influenza pandemic were able to produce antibodies from memory B cells when their blood was exposed to the same strain nine decades later.

The vaccines also trigger the production of T cells. While B cells serve as memory banks to produce antibodies when needed, T cells amplify the body's response to a virus and help recruit cells to attack the pathogen directly. T cells from the vaccine preserve polyfunctionality across the Omicron variant. Memory T cells generated by COVID-19 may last a lifetime, according to a study that examined participants with varying degrees of initial disease severity. Memory T cells generated in individuals who survived a different coronavirus infection in 2003 were shown in a recent paper to last at least 17 years.

Booster shots will just raise antibodies temporarily, but their effectiveness wanes several months later. However, each booster (or exposure) diversifies and broadens T-cell responses to the virus and a booster shot will also expand the potency of B cells, making them better able to respond to Omicron.

During the Omicron variant surge this winter, we did see a greater chance of reinfection compared with previous variants, but not in severe disease across the general population with two-dose vaccines. Booster shots helped older patients achieve greater protection against severe infection, however, and are most critical for those over 65 years of age. Those with any immunocompromising condition should also get additional shots.

Immunocompromised Populations

What is the effectiveness of the vaccines among immunocompromised populations so we can ensure that they are protected? In one large study previously reported by Medscape, COVID-19 vaccine effectiveness was evaluated across a range of patients with rheumatologic conditions on immunosuppressants (ranging from disease-modifying agents to steroids). The mRNA COVID-19 vaccines were highly effective among those on immunosuppressants, although a booster shot is critical to maintain protection.

In another study from Clinical Infectious Diseases , which looked at COVID-19 vaccine responses across a broad range of immunocompromising conditions (eg, hematologic and solid organ malignancies, autoimmune conditions, after solid organ transplants and HIV), only patients on B cell–depleting therapies or solid organ transplant recipients had lower antibody responses to the vaccines.

During the Delta variant era, three doses of an mRNA vaccine gave immunocompromised individuals 87% protection against hospitalization (compared vs 97% for the general population); this study also showed that the Moderna vaccine stimulated a stronger immune response than the Pfizer vaccine, probably due to the former vaccine's higher dose.

Finally, in this large study of those on chemotherapy for solid organ tumors, T-cell responses to the vaccines were maintained at a high level although a boost of antibodies during the treatment is certainly important. Immunocompromised individuals have been approved for a fourth COVID-19 shot and will probably need a booster annually.

To give a personal example of the power of the COVID-19 vaccines, one which I hope will help drive this point home, my 87-year-old father was recently diagnosed with lymphoma. He received three shots of the COVID-19 vaccine before the chemotherapy treatment, and we checked his COVID-19 spike antibodies halfway through the treatment; they were sky high!

Seeing my older immunocompromised father have such a strong immune response to the vaccines during chemotherapy really assured me of the power of these mRNA vaccines. The patient population I treat is those living with HIV, and I reassure them of the power of the mRNA COVID-19 vaccines all the time.

Pre-exposure Prophylaxis and Oral Antivirals

For those who have little immune response to the vaccines (which, as the above studies suggest, is rarer than previously thought, a combination long-acting monoclonal antibody (tixagevimab plus cilgavimab) should be given for pre-exposure prophylaxis. This combination reduces the risk for symptomatic COVID-19 over 6 months by 82.8% with just a single intravenous injection. Finally, the oral antivirals should be easily accessible by those who are immunocompromised in case COVID-19 is acquired, since they will massively reduce the risk for progression in those at risk.

The mRNA vaccines are powerful and have been shown to prevent severe disease across multiple populations. In the future, instead of using an mRNA or DNA vaccine that only exposes us to part of the virus (the spike protein, which is mutated across all the variants), we may need a vaccine booster that exposes us to the entire virus.

There are vaccines which show the host the entire (inactivated) virus combined with an effective adjuvant, which helps improve the immune response to the vaccine. Whole virus vaccines may be more protective against variants with multiple mutations in the spike protein. Vaccines given inside the nose can help boost antibodies at nasal surfaces, which will help with viral transmission.

Therefore, we have many tools to protect even our most vulnerable, including powerful present and coming vaccines, as we learn to live with endemic COVID-19.

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About Dr Monica Gandhi
Monica Gandhi, MD, MPH, is an infectious diseases doctor, professor of medicine, and associate chief in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California, San Francisco (UCSF). She is also director of the UCSF Center for AIDS Research (CFAR) and medical director of the HIV Clinic ("Ward 86") at San Francisco General Hospital. Her research focuses on HIV and women; adherence measurement in HIV treatment and prevention; and, most recently, on how to mitigate the COVID-19 pandemic.

Connect with her on Twitter: @MonicaGandhi9


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