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Prevention With COVID19 Vaccines and Monoclonal Antibodies
Mutations After Mutations: Prevention With COVID-19 Vaccines and Monoclonal Antibodies 

Released: November 20, 2024

Expiration: November 19, 2025

Marcus Pereira
Marcus Pereira, MD, MPH, FAST
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Key Takeaways
  • COVID-19 prevention and vaccines are extremely important aspects of care in immunocompromised patients.
  • Key studies from IDWeek 2024 highlighted the significance of using monoclonal antibodies in COVID-19 prevention, particularly for immunocompromised patients.

Even though there have been no major breakthroughs in the treatment of COVID-19 in the past 2 years, prevention may be another story. Data from IDWeek 2024 suggest that monoclonal antibodies (mAbs) can be used to enhance protection from COVID-19 in patients with immunocompromise. 

Anti-CD20 mAbs
First, I would like to consider a study from Korea that looked at the impact of rituximab, an anti-CD20 therapy, on COVID-19 in patients with immunocompromise. What I found interesting about this study was that among those who received rituximab, vaccine uptake was 69% vs 90% among patients who did not receive it. I am unsure if these results reflect healthcare professionals implying to their patients that they will not respond to the vaccine, or if the patients themselves decided not to bother with the vaccine. Either way, this is concerning.

Unfortunately, patients who received rituximab were disproportionately affected by COVID-19 regardless of whether or not they received the vaccine. Both both people who had and had not received the vaccine had higher rates of SARS-CoV-2 infection and significantly higher rates of hospitalization and all-cause mortality. This highlights a need for additional preventive measures for these patients, particularly those who receive anti-CD20 therapies.

In addition, although previous studies have shown that patients who receive an anti-CD20 therapy are much less likely to respond strongly to the vaccine, the response is not zero. So, one piece of advice that I would give for any patient with immunocompromise is that even if the vaccine response is attenuated, it is still better than not getting vaccinated at all.

Anti–SARS-CoV-2 mAbs
Next, the phase III CANOPY study evaluated pemivibart, a long-acting mAb that targets the SARS-CoV-2 spike protein receptor–binding domain, as pre-exposure prophylaxis in people who were immunocompromised and in people who were at high risk of exposure to COVID-19. This first-in-human study showed that those who received pemivibart had a lower rate of infection and had improvement in their resolution of symptoms compared with people who received a placebo. This demonstrated that there was a protective impact of getting this mAb vs not getting it.

What is unknown about pemivibart is whether it will be effective as the virus mutates. Even though there are mixed data on that topic, I think that for those who are at high risk of severe outcomes, are immunocompromised, or are unlikely to respond fully to the COVID-19 vaccine, pemivibart may still be a good additional intervention. In addition, the long-acting antibody, sipavibart, is under investigation for COVID-19 prophylaxis.

Another first-in-human study assessed a novel mAb, GB0669, with an extended half-life against SARS-CoV-2 and other coronaviruses. In this study, a new mAb was tested for safety and tolerability in healthy volunteers. There was no rate-limiting toxicity, confirming that mAbs in general are safe. However, this study did not show whether there was a sustained and real-life preventive effect. An exploratory analysis of in vitro virus neutralization assays showed efficacy in preventing infection of cells, but clinical trial data demonstrating protection from infection in high-risk and immunocompromised patients are still needed before this novel antibody enters the treatment landscape.

Altogether, we know that COVID-19 is here to stay: It is endemic. So, if patients with immunocompromise do not respond to the vaccine, there will be an ongoing need to develop more protective measures that work for this patient population, including mAbs as pre-exposure prophylaxis. 

New COVID-19 Variants
A major point of discussion in the field of mAbs is how long it will take before the virus mutates away from existing antibodies. Even now, there are some data showing that pemibivart is less effective against new COVID-19 variants. For example, there is a soon-to-be published article looking at in vitro neutralization assays with the newer COVID-19 variants, particularly KP331, showing that pemibivart potentially had reduced activity. However, other studies report that pemibivart remains active against the latest variants. So, the way I interpret these data is that even if pemibivart has reduced activity, it still has some activity, including against other circulating variants apart from KP331.

COVID-19 Vaccine and Transplant Patients
In all, the COVID-19 vaccine remains the best measure for protection. I would strongly encourage transplant patients to get the COVID-19 vaccine, as I think the vaccine is their best chance of mitigating the impact of getting COVID-19, or at least the symptoms of infection. However, mAbs remain a very good additional intervention, particularly in those who are at high risk or are unlikely to respond to the vaccine.

Your Thoughts?
How often are you using mAbs in patients with immunocompromise for the prevention of COVID-19? Get involved in the discussion by commenting about your thoughts below!