Differential immunogenicity of homologous versus heterologous boost in Ad26.COV2.S vaccine recipients

Abstract

Background Protection offered by coronavirus disease 2019 (COVID-19) vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking. Methods We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals (n = 55) who were either primed with Ad26.COV2.S only (n = 13) or were boosted with a homologous (Ad26.COV2.S, n = 28) or heterologous (BNT162b2, n = 14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n = 16) or double (n = 44) dose of BNT162b2. Findings We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals. In contrast, the impact of the homologous boost was quantitatively minimal in Ad26.COV2.S-vaccinated individuals, and Spike-specific antibodies and T cells were narrowly focused to the S1 region. Conclusions Despite the small sample size of the study and the lack of well-defined correlates of protection against COVID-19, the immunological features detected support the utilization of a heterologous vaccine boost in individuals who received Ad26.COV2.S vaccination. Funding This study is partially supported by the Singapore Ministry of Health’s National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001, and COVID19RF-008), The Medical College St. Bartholomew’s Hospital Trustees – Pump Priming Fund for SMD COVID-19 Research.

Omicron reactive multi protein specific CD4 T cells defines cellular immune response induced by inactivated virus vaccines

“…The robust vaccine-induced T cell response was exclusively mediated in inactivated vaccine recipients by CD4 T cells. In contrast, individuals vaccinated with mRNA and non-replicating adenoviral vectored Spike vaccines are capable of inducing both CD4 and CD8 T cell responses as shown previously 10,[49][50][51] , and by our own data. Our results are in contrast with previous observations by other groups that showed the ability of inactivated vaccines to induce both CD4 and CD8 T cell response but are however in line with other data of T cell response observed in other inactivated viral vaccines 52,53 .…”

Humoral and cellular immune memory to four COVID-19 vaccines

“…The hierarchy of the magnitude of the memory CD4 + T cells was mRNA-1273>BNT162b2~NVX-CoV2373>Ad26.COV2.S. These overall findings are consistent with previous reports on COVID-19 vaccine T cell responses (Barouch et al ., 2021; Goel et al ., 2021; Guerrera et al, 2021; Khoo et al, 2022; Liu et al, 2022; Mateus et al ., 2021; Rodda et al, 2022; Tarke et al, 2022), but the analysis reported herein extensively expand these observations, including four different vaccines representing three different vaccine platforms, and with longitudinal data and single-cell cytokine expression resolution providing insights regarding CD4 + T cell subpopulations between the vaccines. Interestingly, multifunctional CD4 + T cells were observed most frequently after mRNA-1273 immunization, and CD4-CTLs represented a substantial fraction of the memory CD4 + T cells after mRNA-1273, BNT162b2, or NVX-CoV2373 vaccination.…”

Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

“…We and others had previously reported enhanced neutralization capacity early after heterologous ChAd-BNT vaccination compared to homologous BNT-BNT-vaccination, both of which in turn induced clearly higher neutralizing antibody titers than a homologous ChAd vaccination regimen [3][4][5][6][7][8][9][10][11][12] . Apart from significant waning of neutralization capacity towards WT virus at late time points for all regimens, we here observed that differences in humoral immunity towards WT virus between ChAd-BNT and BNT-BNT vaccination vanished, while homologous ChAd-ChAd still showed reduced neutralization titers compared to the other two vaccination schemes.…”

“…We and others have previously shown that the heterologous combination of ChAd and mRNA vaccination results in a non-inferior or even superior humoral and cellular immune response compared to homologous mRNA or ChAd vaccination regimens [3][4][5][6][7][8][9][10][11][12] .…”