tetano
Editor, Senior Moderator
EClinicalMedicine
. 2022 Mar 8;45:101323.
doi: 10.1016/j.eclinm.2022.101323. eCollection 2022 Mar.
Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial
Punnee Pitisuttithum[SUP] 1 [/SUP], Viravarn Luvira[SUP] 1 [/SUP], Saranath Lawpoolsri[SUP] 1 [/SUP], Sant Muangnoicharoen[SUP] 1 [/SUP], Supitcha Kamolratanakul[SUP] 1 [/SUP], Chaisith Sivakorn[SUP] 1 [/SUP], Piengthong Narakorn[SUP] 2 [/SUP], Somchaiya Surichan[SUP] 2 [/SUP], Sumalee Prangpratanporn[SUP] 2 [/SUP], Suttida Puksuriwong[SUP] 2 [/SUP], Steven Lamola[SUP] 3 [/SUP], Laina D Mercer[SUP] 3 [/SUP], Rama Raghunandan[SUP] 3 [/SUP], Weina Sun[SUP] 4 [/SUP], Yonghong Liu[SUP] 4 [/SUP], Juan Manuel Carreño[SUP] 4 [/SUP], Rami Scharf[SUP] 3 [/SUP], Weerapong Phumratanaprapin[SUP] 1 [/SUP], Fatima Amanat[SUP] 4 [/SUP], Luc Gagnon[SUP] 5 [/SUP], Ching-Lin Hsieh[SUP] 6 [/SUP], Ruangchai Kaweepornpoj[SUP] 2 [/SUP], Sarwat Khan[SUP] 5 [/SUP], Manjari Lal[SUP] 3 [/SUP], Stephen McCroskery[SUP] 4 [/SUP], Jason McLellan[SUP] 6 [/SUP], Ignacio Mena[SUP] 4 7 [/SUP], Marcia Meseck[SUP] 8 [/SUP], Benjaluck Phonrat[SUP] 1 [/SUP], Yupa Sabmee[SUP] 1 [/SUP], Ratsamikorn Singchareon[SUP] 2 [/SUP], Stefan Slamanig[SUP] 4 [/SUP], Nava Suthepakul[SUP] 2 [/SUP], Johnstone Tcheou[SUP] 4 [/SUP], Narumon Thantamnu[SUP] 1 [/SUP], Sompone Theerasurakarn[SUP] 2 [/SUP], Steven Tran[SUP] 5 [/SUP], Thanakrit Vilasmongkolchai[SUP] 2 [/SUP], Jessica A White[SUP] 3 [/SUP], Nina Bhardwaj[SUP] 8 [/SUP], Adolfo Garcia-Sastre[SUP] 4 7 8 9 [/SUP], Peter Palese[SUP] 4 9 [/SUP], Florian Krammer[SUP] 4 10 [/SUP], Kittisak Poopipatpol[SUP] 2 [/SUP], Ponthip Wirachwong[SUP] 2 [/SUP], Richard Hjorth[SUP] 3 [/SUP], Bruce L Innis[SUP] 3 [/SUP]
Affiliations
Abstract
Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.
Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422).
Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline.
Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2.
Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).
. 2022 Mar 8;45:101323.
doi: 10.1016/j.eclinm.2022.101323. eCollection 2022 Mar.
Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial
Punnee Pitisuttithum[SUP] 1 [/SUP], Viravarn Luvira[SUP] 1 [/SUP], Saranath Lawpoolsri[SUP] 1 [/SUP], Sant Muangnoicharoen[SUP] 1 [/SUP], Supitcha Kamolratanakul[SUP] 1 [/SUP], Chaisith Sivakorn[SUP] 1 [/SUP], Piengthong Narakorn[SUP] 2 [/SUP], Somchaiya Surichan[SUP] 2 [/SUP], Sumalee Prangpratanporn[SUP] 2 [/SUP], Suttida Puksuriwong[SUP] 2 [/SUP], Steven Lamola[SUP] 3 [/SUP], Laina D Mercer[SUP] 3 [/SUP], Rama Raghunandan[SUP] 3 [/SUP], Weina Sun[SUP] 4 [/SUP], Yonghong Liu[SUP] 4 [/SUP], Juan Manuel Carreño[SUP] 4 [/SUP], Rami Scharf[SUP] 3 [/SUP], Weerapong Phumratanaprapin[SUP] 1 [/SUP], Fatima Amanat[SUP] 4 [/SUP], Luc Gagnon[SUP] 5 [/SUP], Ching-Lin Hsieh[SUP] 6 [/SUP], Ruangchai Kaweepornpoj[SUP] 2 [/SUP], Sarwat Khan[SUP] 5 [/SUP], Manjari Lal[SUP] 3 [/SUP], Stephen McCroskery[SUP] 4 [/SUP], Jason McLellan[SUP] 6 [/SUP], Ignacio Mena[SUP] 4 7 [/SUP], Marcia Meseck[SUP] 8 [/SUP], Benjaluck Phonrat[SUP] 1 [/SUP], Yupa Sabmee[SUP] 1 [/SUP], Ratsamikorn Singchareon[SUP] 2 [/SUP], Stefan Slamanig[SUP] 4 [/SUP], Nava Suthepakul[SUP] 2 [/SUP], Johnstone Tcheou[SUP] 4 [/SUP], Narumon Thantamnu[SUP] 1 [/SUP], Sompone Theerasurakarn[SUP] 2 [/SUP], Steven Tran[SUP] 5 [/SUP], Thanakrit Vilasmongkolchai[SUP] 2 [/SUP], Jessica A White[SUP] 3 [/SUP], Nina Bhardwaj[SUP] 8 [/SUP], Adolfo Garcia-Sastre[SUP] 4 7 8 9 [/SUP], Peter Palese[SUP] 4 9 [/SUP], Florian Krammer[SUP] 4 10 [/SUP], Kittisak Poopipatpol[SUP] 2 [/SUP], Ponthip Wirachwong[SUP] 2 [/SUP], Richard Hjorth[SUP] 3 [/SUP], Bruce L Innis[SUP] 3 [/SUP]
Affiliations
- PMID: 35284808
- PMCID: PMC8903824
- DOI: 10.1016/j.eclinm.2022.101323
Abstract
Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.
Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422).
Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline.
Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2.
Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).