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Publications

Journal Article Ahead of print

PubMed: 42168193 DOI: 10.1038/s41541-026-01483-z

Long-term cross-variant Fc-mediated immune responses against SARS-CoV-2 induced by a heterologous adenoviral/inactivated virus prime-boost vaccination strategy.

NPJ Vaccines

Authors: Doyoung Kim, Jung Hyuk Lee, Junhyeon Lee, Ju Yeon Park, Yuna Shin, Soo Ji Kim, BeomMin Cheon, Sumin Lee, Eunjin Cho, Deok Ryun Kim, Ryan P McNamara, Cheol-Heui Yun, Mohamadou Siribie, Asma Binte Aziz, Birkneh Tilahun Tadesse, Florian Marks, Sue Kyoung Jo, Hyon Jin Jeon, Raphaël Rakotozandrindrainy, Ilesh V Jani, Jae Seung Yang, Byoung-Shik Shim, Manki Song

Affiliations

  • International Vaccine Institute, Seoul, Republic of Korea.
  • Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
  • Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
  • Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, USA.
  • Institutes of Green Bio Science & Technology, Seoul National University, Pyeongchang, Republic of Korea.
  • Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
  • Madagascar Institute for Vaccine Research, University of Antananarivo, Antananarivo, Madagascar.
  • Instituto Nacional de Saúde, Maputo, Mozambique.
  • International Vaccine Institute, Seoul, Republic of Korea.
  • International Vaccine Institute, Seoul, Republic of Korea.
  • International Vaccine Institute, Seoul, Republic of Korea.

Abstract

Limited vaccine availability and logistical barriers during the COVID-19 pandemic have hindered homologous boosting in resource-limited regions. Therefore, heterologous prime-boost regimens have gained attention as versatile and practical alternatives. We evaluated the immunogenicity and longevity of four vaccine regimens in adults from Mozambique and Madagascar: single-dose Ad26.COV2.S (Ad26.S), homologous BBIBP-CorV (BBIBP), and two heterologous combinations (BBIBP-Ad26.S and Ad26.S-BBIBP, in prime-boost order). Using systems serology, we characterized Fc-mediated antibody responses against SARS-CoV-2 wild-type and Omicron BA.1. Among all regimens, Ad26.S-BBIBP elicited broad and sustained humoral immunity for up to 6 months, with enhanced IgG levels, Fcγ receptor binding, and Fc-mediated effector functions. These responses declined more slowly than with single-Ad26.S. Compared to the other regimens, antibody-dependent natural killer cell activation (ADNKA) emerged as a distinct characteristic of durable cross-variant immunity in Ad26.S-BBIBP recipients. These findings highlight that the Ad26.S-BBIBP regimen is immunologically advantageous, with Fc-mediated effector functions, particularly ADNKA, representing an important characteristic of its relatively durable and cross-strain protection even as neutralizing antibody titers decline.

MeSH

Sars-Cov-2, Vaccines, Vaccination, Viruses, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus