tetano
Editor, Senior Moderator
Vaccine
. 2026 Sep 4:92:129049.
doi: 10.1016/j.vaccine.2026.129049. Online ahead of print.
Durvanei Augusto Maria 1 , Isabela Mancini Martins 2 , Giselle Pidde Marques Porto 3 , Isadora Maria Villas-Boas 3 , Giovanni Andreu Leite 4 , Letícia de Oliveira Marinho da Silva 4 , Ralyria Mello Vieira Dos Santos 4 , Isabel Maria Vicente Guedes de Carvalho Mello 4 , Silas Fernandes Eto 2 , Mauricio Barbugiani Goldfeder 2 , Regis Edgar Castilho Junior 2 , Giuliana Gaggini Rondon 2 , Morena Brazil Sant'anna 5 , Tamires Cunha Almeida 5 , Douglas Felipe da Silva 5 , Gisele Picolo 5 , Fernanda Faria 2 , Carla Cristina Squaiella Baptistão 3 , Viviane Fongaro Botosso 4 , Esper Georges Kallás 6 ; Non-Clinical Study Working Group; Ana Marisa Chudzinski-Tavassi 7
Affiliations
Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90 days after receiving two intramuscular doses of the H5N8 vaccine (15 μg HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.
Keywords: H5N8 influenza vaccine; Humoral immune response; Non-clinical safety; Oil-in-water adjuvant; Toxicological evaluation.
. 2026 Sep 4:92:129049.
doi: 10.1016/j.vaccine.2026.129049. Online ahead of print.
Safety, humoral and cellular immune responses to a pre-pandemic adjuvanted influenza A (H5N8) vaccine
Durvanei Augusto Maria 1 , Isabela Mancini Martins 2 , Giselle Pidde Marques Porto 3 , Isadora Maria Villas-Boas 3 , Giovanni Andreu Leite 4 , Letícia de Oliveira Marinho da Silva 4 , Ralyria Mello Vieira Dos Santos 4 , Isabel Maria Vicente Guedes de Carvalho Mello 4 , Silas Fernandes Eto 2 , Mauricio Barbugiani Goldfeder 2 , Regis Edgar Castilho Junior 2 , Giuliana Gaggini Rondon 2 , Morena Brazil Sant'anna 5 , Tamires Cunha Almeida 5 , Douglas Felipe da Silva 5 , Gisele Picolo 5 , Fernanda Faria 2 , Carla Cristina Squaiella Baptistão 3 , Viviane Fongaro Botosso 4 , Esper Georges Kallás 6 ; Non-Clinical Study Working Group; Ana Marisa Chudzinski-Tavassi 7
Affiliations
- PMID: 42696822
- DOI: 10.1016/j.vaccine.2026.129049
Abstract
Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90 days after receiving two intramuscular doses of the H5N8 vaccine (15 μg HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.
Keywords: H5N8 influenza vaccine; Humoral immune response; Non-clinical safety; Oil-in-water adjuvant; Toxicological evaluation.