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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月22日

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  • 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

摘要

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.