1. Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge
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Jiyeung Lee, Yun Jeong Na, Min-Suk Song, Young Ki Choi, Chang Geun Lee, Ki Seok Park, So Shin Ahn, Young Ho Byun, Young Chul Sung, Baik Lin Seong, Inhwan Hwang, and Yun Hee Baek
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Prime-boost ,animal diseases ,Mice, Transgenic ,Biology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Injections, Intramuscular ,Virus ,Mice ,Immune system ,Orthomyxoviridae Infections ,Mucosal immunity ,Immunity ,Virology ,medicine ,Influenza A virus ,Animals ,Adenovirus ,H5N2 Avian Influenza Virus ,Immunity, Mucosal ,Administration, Intranasal ,Mice, Inbred BALB C ,Influenza A Virus, H5N1 Subtype ,Body Weight ,Vaccination ,virus diseases ,Influenza A virus subtype H5N1 ,Influenza ,Influenza Vaccines ,Immunology ,Influenza A Virus, H5N2 Subtype ,Vaccine ,Oncovirus - Abstract
Development of effective vaccines against highly pathogenic avian influenza (HPAI) H5N1 viruses is a global public health priority. Considering the difficulty in predicting HPAI H5N1 pandemic strains, one strategy used in their design includes the development of formulations with the capacity of eliciting broad cross-protective immunity against multiple viral antigens. To this end we constructed a replication-defective recombinant adenovirus-based avian influenza virus vaccine (rAdv-AI) expressing the codon-optimized M2eX–HA–hCD40L and the M1-M2 fusion genes from HPAI H5N1 human isolate. Although there were no significant differences in the systemic immune responses observed between the intramuscular prime-intramuscular boost regimen (IM/IM) and the intranasal prime-intramuscular boost regimen (IN/IM), IN/IM induced more potent CD8+ T cell and antibody responses at mucosal sites than the IM/IM vaccination, resulting in more effective protection against lethal H5N2 avian influenza (AI) virus challenge. These findings suggest that the strategies used to induce multi-antigen-targeted mucosal immunity, such as IN/IM delivery of rAdv-AI, may be a promising approach for developing broad protective vaccines that may be more effective against the new HPAI pandemic strains.
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