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

Med. 2022 Feb 11;3(2):104-118.e4. doi: 10.1016/j.medj.2021.12.004. Epub 2022 Jan 19.

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.

Keywords: Adenovirus vector; COVID-19; antiviral immunity; heterologous immunity; vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ad26COVS1*
  • Antibodies, Neutralizing
  • BNT162 Vaccine
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • ChAdOx1 nCoV-19
  • Humans
  • SARS-CoV-2

Substances

  • Ad26COVS1
  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • ChAdOx1 nCoV-19
  • BNT162 Vaccine