Humoral and Cellular Response Following Vaccination With the BNT162b2 mRNA COVID-19 Vaccine in Patients Affected by Primary Immunodeficiencies

Abstract

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.

Safety and Long-Term Immunogenicity of BNT162b2 Vaccine in Individuals with Down Syndrome

“…No patients contracted a SARS-CoV-2 infection up to six months of observation after vaccination. Our results show the vaccine to be highly effective in this population, as measured by antibody levels, with only one individual with DS not seroconverting after the first dose, and compared to other vulnerable populations [11][12][13][14], which showed a suboptimal response to the routine vaccination schedule.…”

“…For the general population, the administration of a two-dose SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccination was found to be safe and effective in immunocompetent individuals [9,10] and was approved for administration in December 2020. However, our group and others have shown that other cohorts of immune-compromised adolescents and young adults, such as solid organ transplanted patients [11,12] and those with primary immune deficiencies [13,14], have a suboptimal immunization with the routine vaccination schedule. In line with this, there is an urgent need to establish an effective immunization schedule against COVID-19 in individuals with DS previously known to have had a B cell dysfunction [5].…”

Common Variable Immunodeficiency Disorders as a Model for Assessing COVID-19 Vaccine Responses in Immunocompromised Patients

“…The most important outcome of COVID-19 vaccination is a balanced, co-ordinated cellular immune response to the virus ( 25 , 30 ). This implies at least some T cell function is required for vaccine efficacy ( 50 ). Given what was noted in the NZHS and NZCS, COVID-19 vaccines will provide at least partial protection in most immunocompromised patients.…”

“…It remains to be determined if heterologous primary immunisation, with mRNA and adenovirus-based vaccines generates a robust cellular response, as seen with humoral responses in healthy individuals ( 58 ). Again, monitoring T cell responses following vaccination will provide reassurance ( 50 , 55 ).…”

“…In patients who are not on SCIG/IVIG, a good antibody response could be interpreted as a satisfactory cellular response to the vaccine. In those who have poor antibody responses, it is still possible they have protective T cell responses ( 50 , 55 ). Many healthy persons failed to seroconvert but had robust T cell responses to SARS-CoV-2 ( 61 ).…”