학술논문

Immunologic Characterization of a Rhesus Macaque H1N1 Challenge Model for Candidate Influenza Virus Vaccine Assessment
Document Type
article
Source
mSphere. 21(12)
Subject
Microbiology
Biological Sciences
Rare Diseases
Vaccine Related
Emerging Infectious Diseases
Immunization
Infectious Diseases
Influenza
Pneumonia & Influenza
Biotechnology
Prevention
Biodefense
Prevention of disease and conditions
and promotion of well-being
3.4 Vaccines
Infection
Good Health and Well Being
Animals
Antibodies
Viral
Humans
Influenza A Virus
H1N1 Subtype
Influenza Vaccines
Influenza
Human
Macaca mulatta
Orthomyxoviridae Infections
Vaccination
Immunology
Language
Abstract
Despite the availability of annually formulated vaccines, influenza virus infection remains a worldwide public health burden. Therefore, it is important to develop preclinical challenge models that enable the evaluation of vaccine candidates while elucidating mechanisms of protection. Here, we report that naive rhesus macaques challenged with 2009 pandemic H1N1 (pH1N1) influenza virus do not develop observable clinical symptoms of disease but develop a subclinical biphasic fever on days 1 and 5 to 6 postchallenge. Whole blood microarray analysis further revealed that interferon activity was associated with fever. We then tested whether type I interferon activity in the blood is a correlate of vaccine efficacy. The animals immunized with candidate vaccines carrying hemagglutinin (HA) or nucleoprotein (NP) exhibited significantly reduced interferon activity on days 5 to 6 postchallenge. Supported by cellular and serological data, we conclude that blood interferon activity is a prominent marker that provides a convenient metric of influenza virus vaccine efficacy in the subclinical rhesus macaque model.