Mucosal immunity induced by adenovirus-based H5N1 HPAI vaccine confers protection against a lethal H5N2 avian influenza virus challenge.
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.
Park
Ki Seok
KS
Laboratory of Cellular Immunology, Division of Molecular and Life Sciences, POSTECH, Pohang 790-784, Republic of Korea.
Lee
Jiyeung
J
Ahn
So Shin
SS
Byun
Young-Ho
YH
Seong
Baik Lin
BL
Baek
Yun Hee
YH
Song
Min-Suk
MS
Choi
Young Ki
YK
Na
Yun Jeong
YJ
Hwang
Inhwan
I
Sung
Young Chul
YC
Lee
Chang Geun
CG
D000281:Administration, Intranasal; D000818:Animals; D001835:Body Weight; D018414:CD8-Positive T-Lymphocytes; D018928:Immunity, Mucosal; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D053125:Influenza A Virus, H5N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D014611:Vaccination
D007252:Influenza Vaccines