PLOS Global Public Health (Jan 2024)

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

  • Catherine Riou,
  • Jinal N Bhiman,
  • Yashica Ganga,
  • Shobna Sawry,
  • Frances Ayres,
  • Richard Baguma,
  • Sashkia R Balla,
  • Ntombi Benede,
  • Mallory Bernstein,
  • Asiphe S Besethi,
  • Sandile Cele,
  • Carol Crowther,
  • Mrinmayee Dhar,
  • Sohair Geyer,
  • Katherine Gill,
  • Alba Grifoni,
  • Tandile Hermanus,
  • Haajira Kaldine,
  • Roanne S Keeton,
  • Prudence Kgagudi,
  • Khadija Khan,
  • Erica Lazarus,
  • Jean Le Roux,
  • Gila Lustig,
  • Mashudu Madzivhandila,
  • Siyabulela F J Magugu,
  • Zanele Makhado,
  • Nelia P Manamela,
  • Qiniso Mkhize,
  • Paballo Mosala,
  • Thopisang P Motlou,
  • Hygon Mutavhatsindi,
  • Nonkululeko B Mzindle,
  • Anusha Nana,
  • Rofhiwa Nesamari,
  • Amkele Ngomti,
  • Anathi A Nkayi,
  • Thandeka P Nkosi,
  • Millicent A Omondi,
  • Ravindre Panchia,
  • Faeezah Patel,
  • Alessandro Sette,
  • Upasna Singh,
  • Strauss van Graan,
  • Elizabeth M Venter,
  • Avril Walters,
  • Thandeka Moyo-Gwete,
  • Simone I Richardson,
  • Nigel Garrett,
  • Helen Rees,
  • Linda-Gail Bekker,
  • Glenda Gray,
  • Wendy A Burgers,
  • Alex Sigal,
  • Penny L Moore,
  • Lee Fairlie

DOI
https://doi.org/10.1371/journal.pgph.0002703
Journal volume & issue
Vol. 4, no. 4
p. e0002703

Abstract

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We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.