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Assessment of the immunogenicity and protection of a Nipah virus soluble G vaccine candidate in mice and pigs.

ABSTRACT: Nipah virus (NiV) is a newly emerged extremely dangerous zoonotic pathogen highly fatal to humans. Currently, no approved vaccine is available against NiV. This study employed a mammalian eukaryotic system to express NiV soluble G glycoprotein (NiV-sG), using CpG oligodeoxynucleotides (CpG)/Aluminum salt (Alum) as adjuvants to obtain a recombinant subunit vaccine candidate. We also evaluated the immunogenicity and efficacy of the protein in mice and pigs. The results showed that humoral and cellular immune responses were induced in all the vaccination groups in two animal models. The levels of specific and neutralizing antibodies and the proliferation levels of T helper(Th) cells were significantly higher than those in the control group. The protective efficacy of the subunit vaccines evaluated in the pseudovirus in vivo infection mouse model strongly suggested that this vaccine could provide protective immunity against NiV. A neoadjuvant (HTa) based on liposomes and cholera toxin combined with CpG/Alum was exploited and evaluated in mice. The neoadjuvant group showed a more protective efficacy than the CpG/Alum group. The aforementioned results indicated that the subunit vaccine could be used as a promising candidate vaccine for preventing Nipah virus infection.

SUBMITTER: Gao Z

PROVIDER: S-EPMC9583134 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Assessment of the immunogenicity and protection of a Nipah virus soluble G vaccine candidate in mice and pigs.

Gao Zihan Z Li Tao T Han Jicheng J Feng Sheng S Li Letian L Jiang Yuhang Y Xu Zhiqiang Z Hao Pengfei P Chen Jing J Hao Jiayi J Xu Peng P Tian Mingyao M Jin Ningyi N Huang Weijin W Li Chang C

Frontiers in microbiology 20221006

Nipah virus (NiV) is a newly emerged extremely dangerous zoonotic pathogen highly fatal to humans. Currently, no approved vaccine is available against NiV. This study employed a mammalian eukaryotic system to express NiV soluble G glycoprotein (NiV-sG), using CpG oligodeoxynucleotides (CpG)/Aluminum salt (Alum) as adjuvants to obtain a recombinant subunit vaccine candidate. We also evaluated the immunogenicity and efficacy of the protein in mice and pigs. The results showed that humoral and cell ...[more]

PMID: 36274696

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Project description:IntroductionImmune correlates of protection afforded by PHV02, a recombinant vesicular stomatitis (rVSV) vector vaccine against Nipah virus (NiV) disease, were investigated in the African green monkey (AGM) model. Neutralizing antibody to NiV has been proposed as the principal mediator of protection against future NiV infection.MethodsTwo approaches were used to determine the correlation between neutralizing antibody levels and outcomes following a severe (1,000 median lethal doses) intranasal/intratracheal (IN/IT) challenge with NiV (Bangladesh): (1) reduction in vaccine dose given 28 days before challenge and (2) challenge during the early phase of the antibody response to the vaccine.ResultsReduction in vaccine dose to very low levels led to primary vaccine failure rather than a sub-protective level of antibody. All AGMs vaccinated with the nominal clinical dose (2 × 107 pfu) at 21, 14, or 7 days before challenge survived. AGMs vaccinated at 21 days before challenge had neutralizing antibodies (geometric mean titer, 71.3). AGMs vaccinated at 7 or 14 days before challenge had either undetectable or low neutralizing antibody titers pre-challenge but had a rapid rise in titers after challenge that abrogated the NiV infection. A simple logistic regression model of the combined studies was used, in which the sole explanatory variable was pre-challenge neutralizing antibody titers. For a pre-challenge titer of 1:5, the predicted survival probability is 100%. The majority of animals with pre-challenge neutralizing titer of ≥1:20 were protected against pulmonary infiltrates on thoracic radiograms, and a majority of those with titers ≥1:40 were protected against clinical signs of illness and against a ≥fourfold antibody increase following challenge (indicating sterile immunity). Controls receiving rVSV-Ebola vaccine rapidly succumbed to NiV challenge, eliminating the innate immunity stimulated by the rVSV vector as a contributor to survival in monkeys challenged as early as 7 days after vaccination.Discussion and conclusionIt was concluded that PHV02 vaccine elicited a rapid onset of protection and that any detectable level of neutralizing antibody was a functional immune correlate of survival.

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Assessment of the immunogenicity and protection of a Nipah virus soluble G vaccine candidate in mice and pigs.

Publications

Assessment of the immunogenicity and protection of a Nipah virus soluble G vaccine candidate in mice and pigs.

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