Recombinant vesicular stomatitis virus–vectored vaccine induces long-lasting immunity against Nipah virus disease

Abstract

The emergence of the novel henipavirus, Langya virus, received global attention earlier this month after the virus sickened over three dozen people in China. There is heightened concern henipaviruses as respiratory pathogens could spark another pandemic, most notably the deadly Nipah virus (NiV). NiV causes near annual outbreaks in Bangladesh and India and induces a highly fatal respiratory disease and encephalitis in humans. No licensed countermeasures against this pathogen exist. An ideal NiV vaccine would confer both fast-acting and long-lived protection.Recently, we reported the generation of a recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the NiV glycoprotein (rVSV-ΔG-NiVBG) that protected 100% of nonhuman primates from NiV-associated lethality within a week. Here, to evaluate the durability of rVSV-ΔG-NiVBG, we vaccinated African green monkeys (AGMs) one year prior to challenge with a uniformly lethal dose of NiV. The rVSV-ΔG-NiVBG vaccine induced stable and robust humoral responses, whereas cellular responses were modest. All immunized AGMs (whether receiving a single dose or prime-boosted) survived with no detectable clinical signs or NiV replication.Transcriptomic analyses indicated adaptive immune signatures correlated with vaccine-mediated protection. While vaccines for certain respiratory infections (e.g., ) have yet to provide durable protection, our results suggest rVSV-ΔG-NiVBG elicits long-lasting immunity.

A vaccine targeting antigen-presenting cells through CD40 induces protective immunity against Nipah disease

“… 22 Other cellular effectors, such as helper and effector T cells, may also participate in host defense. 8 We screened the NiV G ectodomain (ECD) to identify vaccine epitopes using the NetMHC 4.0 and NetMHCII 2.3 software, which predict T cell epitopes that bind to a large panel of class I and II HLA molecules, respectively. Linear B cell epitopes were predicted using the BepiPred 2.0 software.…”

“…Several NiV candidate vaccines are at preclinical or early clinical development stages, but no licensed vaccines or therapeutics are available for human use yet. 7 , 8 , 9 , 10 Most vaccine candidates target the NiV surface glycoprotein (G) and/or fusion (F) protein as immunogens, as these proteins are required for viral entry and are exposed on virus surface. Here, we took advantage of a method to target sequences from these molecules to dendritic cells (DCs).…”

Animal Models for Henipavirus Research

“…As mentioned, the AGM model is the gold standard for both NiV and HeV infection, as it accurately recapitulates human pathogenesis and is amenable to multiple challenge routes, including aerosol. Moreover, a wide range of immunological reagents are available for detailed characterization of the host response [105,107].…”

“…Remdesivir (GS-5734) was also found to be protective [121]. A variety of vaccine countermeasures have been evaluated in the AGM model against NiV and HeV, including rVSV displaying NiV-B (G) glycoprotein [107,122], soluble HeV (G) glycoprotein [109,117], and a chimpanzee adenovirus platform (ChAdOx1) displaying the NiV-M (G) glycoprotein [123]. Thus, the AGM model is versatile and can be used to explore HNV pathogenesis (including neuropathologies) and to develop medical countermeasures.…”

Bibliometric and Temporal Trend Analysis of Nipah Virus- An Emerging Zoonotic Disease: What Do We Know So Far

“…Foster and others have developed a recombinant vesicular stomatitis virus vectorized vaccine against nonhuman primates (monkeys) (49). Woolsey and the team have also reported a recombinant vesicular stomatitis virus-based vaccine against Nipah virus in African green monkeys, and they have observed long-lasting immunity (50). Keshwara and others proposed a Rabies-based vaccine against the Nipah virus (51).…”