RESUMEN
NVX-CoV2373 is an adjuvanted recombinant full-length SARS-CoV-2 spike trimer protein vaccine demonstrated to be protective against COVID-19 in efficacy trials. Here we demonstrate that vaccinated individuals made CD4+ T cell responses after 1 and 2 doses of NVX-CoV2373, and a subset of individuals made CD8+ T cell responses. Characterization of the vaccine-elicited CD8+ T cells demonstrated IFN-γ production. Characterization of the vaccine-elicited CD4+ T cells revealed both circulating T follicular helper (cTfh) cells and Th1 cells (IFN-γ+, TNF-α+, and IL-2+) were detectable within 7 days of the primary immunization. Spike-specific CD4+ T cells were correlated with the magnitude of the later SARS-CoV-2-neutralizing antibody titers, indicating that robust generation of CD4+ T cells, capable of supporting humoral immune responses, may be a key characteristic of NVX-CoV2373 that utilizes Matrix-M adjuvant.
Asunto(s)
COVID-19 , SARS-CoV-2 , Adyuvantes Inmunológicos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Interleucina-2 , Factor de Necrosis Tumoral alfa , Vacunación , Vacunas SintéticasRESUMEN
Vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25-µg Moderna messenger RNA (mRNA)1273 vaccine were examined over the course of 7 months after immunization, including in multiple age groups, with a particular interest in assessing whether preexisting cross-reactive T cell memory affects vaccine-generated immunity. Vaccine-generated spike-specific memory CD4+ T cells 6 months after the second dose of the vaccine were comparable in quantity and quality to COVID-19 cases, including the presence of T follicular helper cells and interferon-γexpressing cells. Spike-specific CD8+ T cells were generated in 88% of subjects, with equivalent memory at 6 months post-boost compared with COVID-19 cases. Lastly, subjects with preexisting cross-reactive CD4+ T cell memory exhibited stronger CD4+ T cell and antibody responses to the vaccine, demonstrating the biological relevance of severe acute respiratory syndrome coronavirus 2cross-reactive CD4+ T cells.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Memoria Inmunológica , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacuna nCoV-2019 mRNA-1273 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Ensayos Clínicos Fase I como Asunto , Reacciones Cruzadas , Humanos , Persona de Mediana Edad , Vacunación , Adulto JovenRESUMEN
Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.