期刊
JOURNAL OF VIROLOGY
卷 95, 期 22, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01321-21
关键词
J paramyxovirus; vaccine
类别
资金
- National Institute of Allergy and Infectious Diseases [R01AI128924]
- Boehringer Ingelheim Animal Health (Merial)
H5N1, a highly pathogenic avian influenza virus, circulates in many Asian countries and a safe and effective vaccine is needed to prevent outbreaks in humans. JPV, a nonsegmented negative-strand RNA virus, has been explored as a promising vaccine vector and has shown efficacy in inducing immune responses in animals. NNSVs like JPV can stably express foreign genes and replicate efficiently in the respiratory tract.
H5N1, an avian influenza virus, is known to circulate in many Asian countries, such as Bangladesh, China, Cambodia, Indonesia, and Vietnam. The current FDA-approved H5N1 vaccine has a moderate level of efficacy. A safe and effective vaccine is needed to prevent outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in humans. Nonsegmented negative-sense single-stranded viruses (NNSVs) are widely used as a vector to develop vaccines for humans, animals, and poultry. NNSVs stably express foreign genes without integrating with the host genome. J paramyxovirus (JPV) is a nonsegmented negative-strand RNA virus and a member of the proposed genus Jeilongvirus in the family Paramyxoviridae. JPV-specific antibodies have been detected in rodents, bats, humans, and pigs, but the virus is not associated with disease in any species other than mice. JPV replicates in the respiratory tract of mice and efficiently expresses the virus-vectored foreign genes in tissue culture cells. In this work, we explored JPV as a vector for developing an H5N1 vaccine using intranasal delivery. We incorporated hemagglutinin (HA) of H5N1 into the JPV genome by replacing the small hydrophobic (SH) gene to generate a recombinant JPV expressing HA (rJPV-Delta SH-H5). A single intranasal administration of rJPV-Delta SH-H5 protected mice from a lethal HPAI H5N1 challenge. Intranasal vaccination of rJPV Delta SH-H5 in rhesus macaques elicited antigen-specific humoral and cell-mediated immune responses. This work demonstrates that JPV is a promising vaccine vector. IMPORTANCE A highly pathogenic avian influenza (HPAI) H5N1 outbreak in Southeast Asia destroyed millions of birds. Transmission of H5N1 into humans resulted in deaths in many countries. In this work, we developed a novel H5N1 vaccine candidate using J paramyxovirus (JPV) as a vector and demonstrated that JPV is an efficacious vaccine vector in animals. Nonsegmented negative-sense single-stranded viruses (NNSVs) stably express foreign genes without integrating into the host genome. JPV, an NNSV, replicates efficiently in the respiratory tract and induces robust immune responses.
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