A new article published on a pre-print server revealed that vaccine efficacy decreased following the use of a single vaccine dose in people who are on the immunosuppressive monoclonal antibody infliximab. The current study included 865 patients on Infliximab, an inhibitor of the tumor necrosis factor (TNF), a potent pro-inflammatory molecule, and 428 patients on vedolizumab, which is an anti-integrin α4β7 monoclonal antibody with selective activity in the gut, but no systemic immunosuppressive effects.
At 3-10 weeks from vaccination, the study showed lower antibodies to the viral spike antigen, as well as lower seroconversion rates, in response to both vaccines, in the infliximab cohort, compared to the other. All these patients had no history of prior infection with the virus. The geometric mean antibody concentrations of anti-spike antibodies in the former were 6 U/mL and 5 U/mL, with the Pfizer and Oxford vaccines, respectively, in the infliximab cohort, compared to 29 U/mL and 14 U/mL, respectively, with vedolizumab.
The findings of this study indicate that for patients on anti-TNF therapy, and especially if an immunomodulator is also used, serological responses to the currently used vaccines are significantly impaired after a single dose.
This could lead to a higher risk of reinfection. When two doses are used, conversely, seroconversion rates are higher, which indicates the need for all such patients to receive both doses as designed, without a delay in the second dose. Moreover, these patients should be considered to be still at risk after a single dose, and should therefore continue to limit their social interactions, and receive shielding, if required.
The absence of seroconversion after two doses was noted in a small fraction of the group, and these patients may need revised vaccine schedules to make sure they mount a protective immune response. Such patients can be identified only by longitudinal measurement of the humoral response. This will also help estimate the durability of vaccine-induced protective antibodies. While these findings agree with recent papers that report the Pfizer vaccine and the Moderna vaccine to be immunogenic in transplant patients and cancer patients on immunosuppressive anti-metabolite drugs, chemotherapy, or immunotherapeutic agents. Here, too, seroconversion was lower among those on immunosuppressants compared to healthy controls.
Two doses led to seroconversion even in tumor patients, but the failure to seroconvert mandates research on how to increase the immunogenicity of the vaccines. Another issue with failed seroconversion in patients on immunosuppressants is the occurrence of chronic infection of the nasal tissues, leading to the emergence of new SARS-CoV-2 variants.