Neutralizing antibody and T cell responses against SARS-CoV-2 variants of concern following ChAdOx-1 or BNT162b2 boosting in the elderly previously immunized with CoronaVac vaccine

Abstract

Background The existence of SARS-CoV-2 variants of concern (VOCs) in association with evidence of breakthrough infections despite vaccination resulted in the need for vaccine boosting. In elderly individuals, information on the immunogenicity of booster vaccinations is limited. In countries where the CoronaVac inactivated vaccine is the primary vaccine, the appropriate boosting regimen is not clear. Immunologic studies of the effects of booster vaccination against VOCs, particularly Delta and Omicron, following CoronaVac in elderly individuals are helpful for policy makers. In this study, we determined the immune responses against VOCs following ChAdOx-1 or BNT162b2 boosting in elderly individuals previously immunized with CoronaVac. Results Before boosting, the median % inhibition of neutralizing antibodies (NAbs) against the wild-type (WT), Alpha, Beta, Delta and Omicron variants in the ChAdOx-1 and BNT162b2 groups was 52.8% vs. 53.4, 36.6% vs. 39.9, 5.2% vs. 13.7, 34.3% vs. 44.9, and 20.8% vs. 18.8%, respectively. After boosting with ChAdOx-1 or BNT162b2, the % inhibition of NAbs were increased to 97.3% vs. 97.4, 94.3% vs. 97.3%, 79.9 vs. 93.7, 95.5% vs. 97.5, and 26.9% vs. 31.9% for WT, Alpha, Beta, Delta and Omicron variants, respectively. Boosting with BNT162b2 induced significantly higher NAb levels than boosting with ChAdOx-1 against the Alpha, Beta and Delta variants but not the WT and Omicron variants. NAb levels against Omicron variant were not significantly different before and after boosting with ChAdOx-1 or BNT162b2. To evaluate T-cell responses, S peptides of the WT, Alpha, Beta and Delta variants were used to stimulate T cells. Upon stimulation, the expression of IL-17A in CD8 T cells was higher in the BNT162b2 group than in the ChAdOx-1 boosting group. However, IFN-γ production in CD4 and CD8 T cells did not significantly differ under all vaccination regimens. The expression of FasL in CD4 T cells, but not CD8 T cells, was higher in the BNT162b2-boosted group. Conclusion Boosting with either ChAdOx-1 or BNT162b2 in CoronaVac-primed healthy elderly individuals induced high NAb production against all examined VOCs except Omicron. BNT162b2 stimulated higher NAb and some T-cell responses than ChAdOx-1. Vaccine boosting is, therefore, recommended for elderly individuals previously immunized with CoronaVac.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19

“…Emerging evidence indicates that rapid and robust immune reactions following infection may mitigate severe progression [24]. Aligning with the critical role for T cell immunity in long-term vaccine protection [25][26][27], our results suggest that COVID-19 vaccines may reduce serious breakthrough infections in seniors with lower CD4 + T cell senescence. For those exceeding the prognostic CD4 + aging threshold, early antiviral or neutralizing antibody treatment may provide effective treatment.…”

COVID-19 vaccination-infection status and immunological profile from India: a case study for prioritizing at risk population for targeted immunization

“…(18) Decay in NAbs over time is well documented and therefore high-risk groups should be boosted with additional doses of vaccines. (19) In our study, serum from individuals with no vaccination or only primary series vaccination had lower neutralization percentage compared to other groups and these groups can potentially benefit from an updated booster dose.…”

Evidence synthesis and pooled analysis of vaccine effectiveness for COVID-19 mRNA vaccine BNT162b2 as a heterologous booster after inactivated SARS-CoV-2 virus vaccines

“…Similar results were observed among studies that pooled data from patients receiving either of the two authorized mRNA vaccines (BNT162b2 and mRNA-1273) as a booster after primary vaccination with an inactivated vaccine. 47 , 48 Additionally, neutralization of SARS-CoV-2 variants, including Alpha, Beta, Delta, Gamma, and Omicron (with exception of one study 44 ), was significantly greater with a heterologous BNT162b2 booster versus a heterologous ChAdOx1 booster after a 2-dose CoronaVac primary series. 17 , 43 , 44 A heterologous BNT162b2 booster after mixed primary regimen of 1-dose CoronaVac and 1-dose ChAdOx1 showed a greater degree of enhancement of humoral and cellular responses and neutralization of Delta and Omicron variants than with a ChAdOx1 booster.…”