Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies

Autor: Ian A. York, Wen-Pin Tzeng, Nedzad Music, Jessica A. Belser, Xiangjie Sun, Min Z. Levine, Ashley Burroughs, Kristy Blanchfield, Ram P. Kamal, Taronna R. Maines, Crystal Holiday
Rok vydání: 2017
Předmět:
0301 basic medicine
Immunology
Influenza A Virus
H7N7 Subtype
influenza pandemics
Neuraminidase
Hemagglutinin (influenza)
Enzyme-Linked Immunosorbent Assay
Hemagglutinin Glycoproteins
Influenza Virus
immunogenicity
Antibodies
Viral
Influenza A Virus
H7N9 Subtype
medicine.disease_cause
Microbiology
Virus
Mice
03 medical and health sciences
Immunogenicity
Vaccine
Influenza A Virus
H1N1 Subtype
Orthomyxoviridae Infections
Virology
Vaccines and Antiviral Agents
medicine
Animals
Hemagglutination assay
H7 avian influenza virus
biology
Influenza A Virus
H3N2 Subtype
Vaccination
Antibody titer
Hemagglutination Inhibition Tests
Influenza A Virus
H7N2 Subtype
Antibodies
Neutralizing
Reverse Genetics
Influenza A virus subtype H5N1
030104 developmental biology
Vaccines
Inactivated
Immunization
Influenza Vaccines
Insect Science
biology.protein
Antibody
influenza
Zdroj: Journal of Virology
ISSN: 1098-5514
0022-538X
Popis: Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody titers measured by hemagglutination inhibition (HI) and virus microneutralization (MN) assays. Since H7 vaccines typically induce low titers in HI and MN assays, they have been considered to be poorly immunogenic. We show that in mice H7 whole inactivated virus vaccines (WIVs) were as immunogenic as seasonal WIVs, as they induced similar levels of overall serum antibodies. However, a larger fraction of the antibodies induced by H7 WIV was nonneutralizing in vitro . Nevertheless, the H7 WIV completely protected mice against homologous viral challenge, and antibodies directed against the HA head were the major contributor toward immune protection. Vaccines against H7 avian influenza viruses may be more effective than HI and virus neutralization assays suggest, and such vaccines may need other methods for evaluation.
Databáze: OpenAIRE
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