Medical countermeasures against henipaviruses: a review and public health perspective

Román, Raúl Gómez; Tornieporth, Nadia; Cherian, Neil George; Shurtleff, Amy C.; Jackson, Maïna L’Azou; Yeskey, Debra; Hacker, Adam; Mungai, Eric; Le, Tung Thanh

doi:10.1016/s1473-3099(21)00400-x

Cited by 17 publications

(11 citation statements)

References 101 publications

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“…These attributes include 1) its ability to transmit via respiratory droplets, 2) its high mutation rate as an RNA virus, 3) its endemicity in regions with high population densities such as communities in South Asia, 4) the extensive geographic range of its natural reservoir (pteropid fruit bats), and 5) the near annual outbreaks of NiV disease occurring in Bangladesh and India (2). For these reasons, NiV is included on the World Health Organization's (WHO) Blueprint List of Priority Pathogens as well as the Coalition for Epidemic Preparedness Innovations (CEPI) Priority Pathogens List (3). In 2020, the US Centers for Disease Control and Prevention (CDC) proposed adding NiV to the Tier 1 Select Agent list due to its bioweapon potential (4); currently, NiV remains a non-Tier 1 CDC and US Department of Agriculture (USDA) Select Agent (5).…”

Section: Introductionmentioning

confidence: 99%

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

Woolsey¹,

Borisevich²,

Fears³

et al. 2023

Journal of Clinical Investigation

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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.

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Section: Introductionmentioning

confidence: 99%

“…3 PFU of NiVB i.n. dose delivered by MAD.Post-exposure blood samples were collected at 4, 7, 10, 14, 21, 28, terminally, and/or 35 days.Blue pins indicate vaccination phase sampling timepoints, whereas red lines denote challenge phase sampling timepoints.…”

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confidence: 99%

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

Woolsey¹,

Borisevich²,

Fears³

et al. 2023

Journal of Clinical Investigation

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“…Although multiple reviews have highlighted the preclinical development of numerous NiV vaccine candidates [1,2,13,[16][17][18], limited research has focused on evaluating the progress of vaccine candidates that have advanced and are currently undergoing assessment in clinical trials. Additionally, there are few review studies assessing current progress towards the development of monoclonal antibodies (mAbs), which can fulfil a different, though complementary role to vaccines as part of prevention strategies.…”

Section: Introductionmentioning

confidence: 99%

Current progress towards prevention of Nipah and Hendra disease in humans: A scoping review of vaccine and monoclonal antibody candidates being evaluated in clinical trials

Rodrigue,

Gravagna,

Yao

et al. 2024

Tropical Med Int Health

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ObjectivesNipah and Hendra are deadly zoonotic diseases with pandemic potential. To date, no human vaccine or monoclonal antibody (mAb) has been licensed to prevent disease caused by these pathogens. The aim of this scoping review was to identify and describe all Phase I, II, and III clinical trials of vaccine candidates or mAbs candidates designed to prevent Nipah and Hendra in humans and to compare the characteristics of the vaccine candidates to characteristics outlined in the Target Product Profile drafted by the World Health Organisation as part of the WHO Research & Development Blueprint for Action to Prevent Epidemics.MethodsWe searched 23 clinical trial registries, the Cochrane Central Register of Clinical Trials, and grey literature up to June 2023 to identify vaccine and mAb candidates being evaluated in registered clinical trials. Vaccine candidate and trial characteristics were double‐extracted for evaluation and the vaccine candidate characteristics were compared with the preferred and critical criteria of the World Health Organisation's Target Product Profile for Nipah virus vaccine.ResultsThree vaccine candidates (Hendra Virus Soluble Glycoprotein Vaccine [HeV‐sG‐V], PHV02, and mRNA‐1215) and one mAb (m102.4) had a registered human clinical trial by June 2023. All trials were phase 1, dose‐ranging trials taking place in the United States of America or Australia and enrolling healthy adults. Although all vaccine candidates meet the dose regimen and route of administration criteria of the Target Product Profile, other criteria such as measures of efficacy and reactogenicity will need to be evaluated in the future as evidence becomes available.ConclusionMultiple vaccine candidates and one mAb candidate have reached the stage of human clinical trials and are reviewed here. Monitoring progress during evaluation of these candidates and candidates entering clinical trials in the future can help highlight many of the challenges that remain.

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“…Despite NiV outbreaks occurring almost annually and the pandemic potentiality of the virus, no vaccines or therapeutics have yet been approved and made available for human use [28][29][30]. Vaccines in general are targeted to induce humoral immunity, specifically protective antibodies; recent vaccine development also aims to generate cellular immunity.…”

Section: Introductionmentioning

confidence: 99%

The Immunobiology of Nipah Virus

et al. 2022

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Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that emerged in Malaysia in 1998. It is a human pathogen capable of causing severe respiratory infection and encephalitis. The natural reservoir of NiV, Pteropus fruit bats, remains a continuous virus source for future outbreaks, although infection in the bats is largely asymptomatic. NiV provokes serious disease in various mammalian species. In the recent human NiV outbreaks in Bangladesh and India, both bats-to-human and human-to-human transmissions have been observed. NiV has been demonstrated to interfere with the innate immune response via interferon type I signaling, promoting viral dissemination and preventing antiviral response. Studies of humoral immunity in infected NiV patients and animal models have shown that NiV-specific antibodies were produced upon infection and were protective. Studies on cellular immunity response to NiV infection in human and animal models also found that the adaptive immune response, specifically CD4+ and CD8+ T cells, was stimulated upon NiV infection. The experimental vaccines and therapeutic strategies developed have provided insights into the immunological requirements for the development of successful medical countermeasures against NiV. This review summarizes the current understanding of NiV pathogenesis and innate and adaptive immune responses induced upon infection.

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Medical countermeasures against henipaviruses: a review and public health perspective

Cited by 17 publications

References 101 publications

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

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

Current progress towards prevention of Nipah and Hendra disease in humans: A scoping review of vaccine and monoclonal antibody candidates being evaluated in clinical trials

The Immunobiology of Nipah Virus

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