medwireNews: Delaying the third dose of vaccines against SARS-CoV-2 until B-cell repopulation may warrant investigation as a strategy to improve response rates among rituximab-treated patients, suggest findings from a small study.
Jacques-Eric Gottenberg and colleagues, from Strasbourg University Hospital in France, evaluated humoral and cellular immune responses to vaccination in 10 rituximab-treated individuals, of whom nine had rheumatoid arthritis and one had stiff-person syndrome. Participants were a median age of 72 years and had received a median of five rituximab cycles, with a median of 227 days between the last rituximab infusion and the first vaccine dose.
As reported in a comment published in The Lancet Rheumatology, 30% of patients were seronegative for anti-SARS-CoV-2 antibodies after their second vaccine dose, and these people remained seronegative 1 month after their third dose, with “only a slightly increased T-cell response” compared with just before their third dose.
Just one patient had neutralizing anti-SARS-CoV-2 antibodies after their second vaccine dose, but an additional three developed neutralizing antibodies following the third dose. These three people were previously seropositive but did not have detectable neutralizing antibodies after their second dose. One patient who was seropositive but did not have a detectable T-cell response before their third dose developed a T-cell response afterwards.
These findings suggest that the third dose may help people with an antibody response after the second dose to “to acquire a neutralizing antibody response or to develop a T-cell response, or both,” say Gottenberg and team.
They stress, however, that “[a]ll seronegative patients […] with B-cell depletion after two doses remained seronegative after the third dose.”
In a further evaluation of the association between B-cell counts and vaccine response, the researchers found that people who were seropositive after the third dose (n=7) “generally had more circulating B cells” at the time the third dose was administered than those who were seronegative after (n=3), with median counts of 36 and 0 cells/μL, respectively.
Moreover, there was a significant positive correlation between B-cell count at the time of the third vaccine dose and neutralizing antibody concentrations 1 month later.
Although these results require confirmation in larger studies, they “support delaying the third dose of SARS-CoV-2 vaccine until B-cell repopulation,” write the study authors.
They say that a number of “crucial questions” remain to be addressed in seronegative patients treated with rituximab. These include whether isolated cell-mediated responses confer protection against COVID-19, and what the optimal strategy is “between waiting for B-cell repopulation, prophylactive anti-SARS-CoV-2 monoclonal antibody therapy in those who are highly immunocompromised […] or curative anti-SARS-CoV-2 monoclonalantibody therapy in cases of SARS-CoV-2 infection.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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