Antibody and T-cell responses to coronavirus disease 2019 vaccination in common variable immunodeficiency and specific antibody deficiency.

BACKGROUND: Clinical trials of the mRNA coronavirus disease 2019 (COVID-19) vaccines excluded individuals with primary antibody deficiencies. OBJECTIVE: To evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with common variable immunodeficiency (CVID) and specific antibody deficiency (SAD) were comparable to those in healthy controls. METHODS: We measured antibody responses against the spike glycoprotein and the receptor-binding domain (RBD) in addition to severe acute respiratory syndrome coronavirus 2 specific T-cell responses using peripheral blood mononuclear cells 2 to 8 weeks after the subjects completed the primary 2-dose vaccine series. RESULTS: The study comprised 12 patients with CVID, 7 patients with SAD, and 10 controls. Individuals with CVID had lower immunoglobulin (Ig) G and Ig A levels against spike glycoprotein than did both individuals with SAD (P = .27 and P = .01, respectively) and controls (P = .01 and P = .004, respectively). The CVID group developed lower IgG titers against the RBD epitope than did the control group (P = .01). Participants with CVID had lower neutralizing titers than did the control group (P = .002). All participants with SAD developed neutralizing titers. All 3 groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination. CONCLUSION: Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, whereas patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.

Antibody and T-cell responses to COVID-19 Vaccination in Common Variable Immunodeficiency and Specific Antibody Deficiency

Background Clinical trials of the mRNA COVID-19 vaccines excluded individuals with primary antibody deficiencies. Objective The aim of this study was to evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with Common Variable Immunodeficiency (CVID) and Specific Antibody Deficiency (SAD) were comparable to healthy controls. Methods We measured antibody responses against the S protein and the receptor binding domain (RBD) as well as SARS-CoV2 specific T-cell responses using peripheral blood mononuclear cells (PBMCs) 2-8 weeks after subjects completed the primary 2-dose vaccine series. Results 12 patients with CVID, 7 patients with SAD, and 10 controls were included in the study. Individuals with CVID had lower IgG and IgA levels against S protein compared to both individuals with SAD (p= 0.27 and p=0.01, respectively) and as well as to controls (p=0.012 and p=0.004, respectively). The CVID group developed lower IgG titers against the RBD epitope compared to the control group (p=0.014). CVID participants had lower neutralizing titers compared to the control group (p=0.002). All SAD participants developed neutralizing titers. All three of our groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination. Conclusion Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, while patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.

SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells.

Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8+ cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8+ T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR - TNF - NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription. T-cells specific for the early gene-product HIV-Nef uniquely increased in frequency and acquired effector function (granzyme-B) in ART-treated individuals following SARS-CoV-2 mRNA vaccination. These parameters of CD8+ T-cell induction correlated with significant decreases in cell-associated HIV mRNA, suggesting killing or suppression of cells transcribing HIV. Thus, we report the observation of an intervention-induced reduction in a measure of HIV persistence, accompanied by precise immune correlates, in ART-suppressed individuals. However, we did not observe significant depletions of intact proviruses, underscoring challenges to achieving (or measuring) HIV reservoir reductions. Overall, our results support prioritizing the measurement of granzyme-B-producing Nef-specific responses in latency reversal studies and add impetus to developing HIV-targeted mRNA therapeutic vaccines that leverage built-in LRA activity.