tetano
Editor, Senior Moderator
J Virol. 2014 May 7. [Epub ahead of print]
African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates.
Matsuoka Y1, Suguitan A Jr, Orandle M, Paskel M, Boonnak K, Gardner DJ, Feldmann F, Feldmann H, Marino M, Jin H, Kemble G, Subbarao K.
Author information
Abstract
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 humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative 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 non-human primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) 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 pattern and site 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 intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects, and that AGMs may be useful model to evaluate the replication of ca vaccine candidates.
IMPORTANCE:
Ferrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we experienced significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a non-human primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans, and that AGMs can be useful for evaluation of the protective efficacy of pLAIV.
PMID:
24807726
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24807726
African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates.
Matsuoka Y1, Suguitan A Jr, Orandle M, Paskel M, Boonnak K, Gardner DJ, Feldmann F, Feldmann H, Marino M, Jin H, Kemble G, Subbarao K.
Author information
Abstract
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 humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative 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 non-human primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) 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 pattern and site 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 intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects, and that AGMs may be useful model to evaluate the replication of ca vaccine candidates.
IMPORTANCE:
Ferrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we experienced significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a non-human primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans, and that AGMs can be useful for evaluation of the protective efficacy of pLAIV.
PMID:
24807726
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24807726