Influenza vaccines promote humoral and cellular immune responses: a randomized, double-blind, phase 3 trial

Annual vaccination is an effective strategy for preventing severe disease caused by seasonal influenza. Quadrivalent influenza vaccines (QIVs) protect against two strains of influenza A and two strains of influenza B, thereby enhancing the host antiviral neutralizing antibody response and inducing CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses. Here, we report findings from a randomized, double-blind, active-controlled phase 3 clinical trial (NCT05431725) that includes 334 healthy adults aged 18-64 years and evaluates the humoral and cellular antiviral immune responses induced by two inactivated QIVs, Sinovac-QIV and Vaxigrip-Tetra™. The primary endpoint of the study is the specific antibody responses measured by hemagglutination inhibition (HAI) assays 28 days post-vaccination, while the secondary endpoint is virus-specific T cell responses. Both QIVs elicit significant increases in antibody titers 28 days after vaccination; Sinovac-QIV induces 9-10-fold increases in geometric mean titers, while Vaxigrip-Tetra™ elicits 7-8-fold increases (p < 0.05). Cellular immune responses using ELISPOT and supervised and unsupervised flow cytometry analyses show that both vaccines modulate the frequency of hemagglutinin-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell subsets, inducing distinct T cell response profiles. Although cellular analyses are evaluated in a subgroup of the cohort, the data indicate that both QIVs induce robust humoral and cellular immunity in adults, providing mechanistic insights into vaccine-induced protection.

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Journal
Nature Communications
Published
2025-12-07
DOI
https://doi.org/10.1038/s41467-025-67102-y
Citations
1
Primary Topic
Influenza Virus Research Studies
Type
article
Field-Weighted Citation Impact
1.35

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Influenza vaccines promote humoral and cellular immune responses: a randomized, double-blind, phase 3 trial

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Influenza vaccines promote humoral and cellular immune responses: a randomized, double-blind, phase 3 trial

Hernán F. Peñaloza, Lester J. Pérez, Pablo A. González, Susan M. Bueno, Linmar Rodríguez‐Guilarte, Maite Oyonarte, Qianqian Xin, Loreto Twele, Andrea Schilling, Alex Cabrera, Leandro J. Carreño, Mariana Ríos, Constanza Méndez, Alexis M. Kalergis, Sofía Aljaro, José Vicente González-Aramúndiz, Cristián Gutiérrez-Vera, Milena Villarroel, Diana Campos, Wanqi Yang, Daniela Moreno‐Tapia, Rosa Feijoo, Pía Smok Vásquez, Álvaro Rojas, P. Jara, Mario Calvo, María Javiera Álvarez-Figueroa, Constanza Del Río, Marisa Domínguez, Andrea Castejón, Silvana Grandón, Francisca Bascur, Patricio Astudillo, François S. Roman, Carlos M. Pérez, Pablo A Palacios, Daniela Rivera, Antonia Reyes
article en
1 citations

Abstract

Annual vaccination is an effective strategy for preventing severe disease caused by seasonal influenza. Quadrivalent influenza vaccines (QIVs) protect against two strains of influenza A and two strains of influenza B, thereby enhancing the host antiviral neutralizing antibody response and inducing CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses. Here, we report findings from a randomized, double-blind, active-controlled phase 3 clinical trial (NCT05431725) that includes 334 healthy adults aged 18-64 years and evaluates the humoral and cellular antiviral immune responses induced by two inactivated QIVs, Sinovac-QIV and Vaxigrip-Tetra™. The primary endpoint of the study is the specific antibody responses measured by hemagglutination inhibition (HAI) assays 28 days post-vaccination, while the secondary endpoint is virus-specific T cell responses. Both QIVs elicit significant increases in antibody titers 28 days after vaccination; Sinovac-QIV induces 9-10-fold increases in geometric mean titers, while Vaxigrip-Tetra™ elicits 7-8-fold increases (p < 0.05). Cellular immune responses using ELISPOT and supervised and unsupervised flow cytometry analyses show that both vaccines modulate the frequency of hemagglutinin-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell subsets, inducing distinct T cell response profiles. Although cellular analyses are evaluated in a subgroup of the cohort, the data indicate that both QIVs induce robust humoral and cellular immunity in adults, providing mechanistic insights into vaccine-induced protection.

Nature CommunicationsVol. 17(1)
Universidad del Desarrollo (CL), Pontificia Universidad Católica de Chile (CL), Austral University of Chile (CL), Clínica Alemana (CL), Sinovac Biotech (CN), San Sebastián University (CL), European Molecular Biology Laboratory (DE), Millennium Institute on Immunology and Immunotherapy (CL), University of Chile (CL)
Institut Català de Nanociència i Nanotecnologia, Instituto Milenio en Inmunología e Inmunoterapia, Agencia Nacional de Investigación y Desarrollo
Openalex Percentile: Top 13%
Influenza Virus Research Studies
1.35
DOIOpen Access PDFOpenAlex
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