Publication: African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates
No. of Pages/File Size
Journal of Virology. Vol.88, No.14 (2014), 8139-8152
Yumiko Matsuoka, Amorsolo Suguitan, Marlene Orandle, Myeisha Paskel, Kobporn Boonnak, Donald J. Gardner, Friederike Feldmann, Heinz Feldmann, Michael Marino, Hong Jin, George Kemble, Kanta Subbarao (2014). African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/34084.
African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates
Live attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of the wt viruses replicated efficiently, while replication of the ca vaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2 ca vaccines. Protection from wt virus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication of ca vaccine candidates. © 2014, American Society for Microbiology.