Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

Post-Vaccination Anti-SARS-CoV-2-Antibody Response in Patients with Multiple Myeloma Correlates with Low CD19+ B-Lymphocyte Count and Anti-CD38 Treatment

“…Furthermore, being on any treatment was associated with a lower titer [32]. Nonetheless, younger age as a negatively impacting factor is not restricted to hematological patients but is also observed in healthy individuals [29,30]. Our results are paralleled by those currently reported by Pimpinelli et al who observed lower levels of anti-SARS-CoV-2 SP-AbT in 42 patients with MM (median age 73 years) who were vaccinated twice with BNT162b2.…”

“…In a comparison of cancer patients to healthy controls after the first vaccination with BNT162b2, Monin-Aldama et al described rates of seroconversion of 97, 39, and 13% in healthy controls, solid cancer patients, and patients with hematological malignancies, respectively [26]. Indeed, high seroconversion rates of about 95% for healthy individuals after the first vaccination have been confirmed by others across different vaccine types, but with lower antibody titers in older individuals [27][28][29][30].…”

Low neutralizing antibody responses in WM, CLL and NHL patients after the first dose of the BNT162b2 and AZD1222 vaccine

“…Our results also suggest that a second timely vaccine dose is necessary for patients with hematological malignancies that deregulate the immune homeostasis, and especially for the elderly [21]. A shorter time interval between the two doses of the AZD1222 would be relevant, as well [22].…”

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

“…Although vaccines have been available since early 2021, achieving near universal coverage has in adults has been an immense logistical challenge, in particular for populous nations where B.1.617.2 is growing rapidly with considerable morbidity and mortality 11 . Current vaccines were designed to target the B.1, Wuhan-1 virus, and the emergence of variants with reduced susceptibility to vaccines such as B.1.351 and P.1 has raised fears for longer term control and protection through vaccination 12,13 , particularly in risk groups 14,15 . The specific reasons behind the explosive global growth of B.1.617.2 in populations remain unclear.…”