Lancet (London, England) · 2025
Safety and immunogenicity of a Nipah virus vaccine (HeV-sG-V) in adults: a single-centre, randomised, observer-blind, placebo-controlled, phase 1 study.
СтатьяКлиническое исследование I фазыРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Frenck Robert W, Naficy Abdi, Feser Jodi, Dickey Michelle P, Leyva-Grado Victor H, Egan Michael A, Chen Tracy, Eldridge John H, Sciotto-Brown Susan, Hermida Luz, Promeneur Dominique, Luckay Amara, Medina Herbert, Lazaro Glorie-Grace A, Patel Nairuti R, Naqvi Tahira, Broder Christopher C, Dimitrov Antony S, Gast Chris, Mercer Laina D, Raine Mike, Andi-Lolo Indah, Innis Bruce L, Aponte John J, Hamm Stefan, Rathi Niraj
Аннотация
BACKGROUND: First discovered in 1999 in Malaysia, Nipah virus (NiV) causes yearly outbreaks throughout south and southeast Asia with associated mortality rates of 40-75%. Due to the structural and sequence similarities between the NiV and Hendra virus (HeV) attachment G glycoproteins, and the extensive extant evidence of the ability of a recombinant soluble glycoprotein G (HeV-sG) to provide heterologous cross-protective immunity when used as vaccine (HeV-sG-V), this study aimed to evaluate HeV-sG-V for safety, tolerability, and immunogenicity against NiV.
METHODS: We conducted a phase 1, single-centre, randomised, observer-blind, placebo-controlled study. Eligible participants were aged 18-49 years, healthy, and not pregnant; participants were ineligible if they were immunocompromised, had received blood products within 6 months of enrolment, had potential exposure to NiV or HeV, or had known allergies to components of the vaccine. Participants were randomly assigned in a 5:1 ratio to receive either one or two doses of the vaccine candidate (at 10 μg for the first cohort; 30 μg at days 1 and either days 8 or 29 for cohort 2; and 100 μg with the same timing for cohort 3) or placebo. The primary endpoints were solicited and unsolicited adverse events, clinically significant laboratory test result abnormalities, medically attended adverse events, and serious adverse events. Secondary endpoints were serum IgG binding via ELISA and neutralising antibody responses against prototypical NiV Bangladesh (NiVB) and NiV Malaysia (NiVM) reporter viruses.
FINDINGS: Between Feb 24, 2020, and Oct 6, 2021, 268 participants were screened, and 192 were enrolled. 173 (90%) participants met the per-protocol criteria. Mild-to-moderate injection site pain was the most commonly reported adverse event. No serious adverse events, hospitalisations, or deaths were reported. The immune response to HeV-sG-V was dose-dependent; a single administration was not sufficiently immunogenic, whereas two administrations were immunogenic, with the highest response rates observed among vaccinees that received two administrations of the 100 μg HeV-sG-V 28 days apart (neutralising antibody geometric mean titres rose dramatically 7 days after the second investigational product dose, reaching 1485·6 (990·5-2228·1) and 2581·9 (147·1-3194·2) for NiVB and NiVM, respectively).
INTERPRETATION: All three doses and regimens of HeV-sG-V had a tolerable risk profile and were able to induce an immune response. The induction of antibodies within 1 month of vaccination, along with the persistence afforded by two dosages, suggests the vaccine candidate has potential for reactive outbreak control and preventive use.
FUNDING: Coalition for Epidemic Preparedness Innovations (CEPI).
METHODS: We conducted a phase 1, single-centre, randomised, observer-blind, placebo-controlled study. Eligible participants were aged 18-49 years, healthy, and not pregnant; participants were ineligible if they were immunocompromised, had received blood products within 6 months of enrolment, had potential exposure to NiV or HeV, or had known allergies to components of the vaccine. Participants were randomly assigned in a 5:1 ratio to receive either one or two doses of the vaccine candidate (at 10 μg for the first cohort; 30 μg at days 1 and either days 8 or 29 for cohort 2; and 100 μg with the same timing for cohort 3) or placebo. The primary endpoints were solicited and unsolicited adverse events, clinically significant laboratory test result abnormalities, medically attended adverse events, and serious adverse events. Secondary endpoints were serum IgG binding via ELISA and neutralising antibody responses against prototypical NiV Bangladesh (NiVB) and NiV Malaysia (NiVM) reporter viruses.
FINDINGS: Between Feb 24, 2020, and Oct 6, 2021, 268 participants were screened, and 192 were enrolled. 173 (90%) participants met the per-protocol criteria. Mild-to-moderate injection site pain was the most commonly reported adverse event. No serious adverse events, hospitalisations, or deaths were reported. The immune response to HeV-sG-V was dose-dependent; a single administration was not sufficiently immunogenic, whereas two administrations were immunogenic, with the highest response rates observed among vaccinees that received two administrations of the 100 μg HeV-sG-V 28 days apart (neutralising antibody geometric mean titres rose dramatically 7 days after the second investigational product dose, reaching 1485·6 (990·5-2228·1) and 2581·9 (147·1-3194·2) for NiVB and NiVM, respectively).
INTERPRETATION: All three doses and regimens of HeV-sG-V had a tolerable risk profile and were able to induce an immune response. The induction of antibodies within 1 month of vaccination, along with the persistence afforded by two dosages, suggests the vaccine candidate has potential for reactive outbreak control and preventive use.
FUNDING: Coalition for Epidemic Preparedness Innovations (CEPI).