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

tetano

Editor, Senior Moderator
Nat Commun


. 2025 Dec 7.
doi: 10.1038/s41467-025-67102-y. Online ahead of print. Influenza vaccines promote humoral and cellular immune responses: a randomized, double-blind, phase 3 trial

Linmar Rodríguez-Guilarte[SUP] 1 2 [/SUP], Constanza Méndez[SUP] 1 2 [/SUP], Antonia Reyes[SUP] 1 2 [/SUP], Mariana Rios[SUP] 1 2 [/SUP], Francisca Román[SUP] 1 2 [/SUP], Daniela Moreno-Tapia[SUP] 1 2 [/SUP], Alex Cabrera[SUP] 2 3 4 [/SUP], Daniela B Rivera[SUP] 1 2 [/SUP], Cristián Gutiérrez-Vera[SUP] 1 5 [/SUP], Pablo A Palacios[SUP] 1 5 [/SUP], Andrea Schilling[SUP] 6 [/SUP], Sofia Aljaro[SUP] 6 7 [/SUP], Francisca Bascur[SUP] 6 [/SUP], Álvaro Rojas[SUP] 7 [/SUP], Constanza Del Río[SUP] 7 [/SUP], Patricio Astudillo[SUP] 7 [/SUP], Carlos M Perez[SUP] 8 [/SUP], Loreto Perez[SUP] 8 [/SUP], Maite Oyonarte[SUP] 9 [/SUP], Patricia E Fernández Vásquez[SUP] 9 [/SUP], Rosa M Feijoo[SUP] 9 [/SUP], Daniel Beltrán Campos[SUP] 10 11 [/SUP], Carlos Tovar De Sousa[SUP] 10 11 [/SUP], Andrea Castejón[SUP] 10 11 [/SUP], Silvana Grandón[SUP] 10 11 [/SUP], Marcela Villarroel[SUP] 10 11 [/SUP], Pía Jara[SUP] 10 11 [/SUP], Loreto Twele[SUP] 10 11 [/SUP], M Angélica Domínguez[SUP] 12 [/SUP], José V González-Aramundiz[SUP] 13 [/SUP], María Javiera Álvarez-Figueroa[SUP] 13 [/SUP], Wanqi Yang[SUP] 14 [/SUP], Qianqian Xin[SUP] 15 [/SUP], Leandro J Carreño[SUP] 1 5 [/SUP], Mario Calvo[SUP] 1 16 [/SUP], Susan M Bueno[SUP] 1 2 [/SUP], Hernán F Peñaloza[SUP] 17 18 19 [/SUP], Pablo A González[SUP] 20 21 [/SUP], Alexis M Kalergis[SUP] 22 23 24 [/SUP]



Affiliations
Free article 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.


 
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