Immunogenicity and reactogenicity of booster vaccinations after Ad26.COV2.S priming

  1. R.S.G. Sablerolles
  2. W.J.R. Rietdijk
  3. A. Goorhuis
  4. D.F. Postma
  5. L.G. Visser
  6. D. Geers
  7. K.S. Schmitz
  8. H.M. Garcia Garrido
  9. M.P.G. Koopmans
  10. V.A.S.H. Dalm
  11. N.A. Kootstra
  12. A.L.W. Huckriede
  13. M. Lafeber
  14. D. van Baarle
  15. C.H. GeurtsvanKessel
  16. R.D. de Vries
  17. P.H.M. van der Kuy
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Abstract

Background

In face of the developing COVID-19 pandemic with a need for rapid and practical vaccination strategies, Ad26.COV2.S was approved as single shot immunization regimen. While effective against severe COVID-19, Ad26.COV2.S vaccination induces lower SARS-CoV-2-specific antibody levels compared to its mRNA-based counterparts. To support decision making on the need for booster vaccinations in Ad26.COV2.S-primed individuals, we assessed the immunogenicity and reactogenicity of homologous and heterologous booster vaccinations in Ad26.COV2.S-primed health care workers (HCWs).

Methods

The SWITCH trial is a single-(participant)-blinded, multi-center, randomized controlled trial among 434 HCWs who received a single Ad26.COV2.S vaccination. HCWs were randomized to no boost, Ad26.COV2.S boost, mRNA-1273 boost, or BNT162b2 boost. We assessed the level of SARS-CoV-2-specific binding antibodies, neutralizing antibodies against infectious virus, SARS-CoV-2-specific T-cell responses, and reactogenicity.

Results

Homologous and heterologous booster vaccinations resulted in an increase in SARS-CoV-2-specific binding antibodies, neutralizing antibodies and T-cell responses when compared to single Ad26.COV.2.S vaccination. In comparison with the homologous boost, the increase was significantly larger in heterologous regimens with the mRNA-based vaccines. mRNA-1273 boosting was most immunogenic, associated with higher reactogenicity. Only mild to moderate local and systemic reactions were observed on the first two days following booster.

Conclusions

Boosting of Ad26.COV2.S-primed HCWs was well-tolerated and immunogenic. Strongest responses were detected after boosting with mRNA-based vaccines. Based on our data, efficacy on infection and transmission of boosters is expected. In addition to efficacy, decision making on boost vaccinations should include timing, target population, level of SARS CoV-2 circulation, and the global inequity in vaccine access.

Trial registration

Funded by ZonMW (10430072110001);<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link>number,<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04927936">NCT04927936</ext-link>.

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