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

Pitisuttithum, Punnee; Luvira, Viravarn; Lawpoolsri, Saranath; Muangnoicharoen, Sant; Kamolratanakul, Supitcha; Sivakorn, Chaisith; Narakorn, Piengthong; Surichan, Somchaiya; Prangpratanporn, Sumalee; Puksuriwong, Suttida; Lamola, Steven; Mercer, Laina D.; Raghunandan, Rama; Sun, Weina; Liu, Yonghong; Carreño, Juan Manuel; Scharf, Rami; Phumratanaprapin, Weerapong; Amanat, Fatima; Gagnon, Luc; Hsieh, Ching-Lin; Kaweepornpoj, Ruangchai; Khan, Sarwat; Lal, Manjari; McCroskery, Stephen; McLellan, Jason S.; Mena, Ignacio; Meseck, Marcia; Phonrat, Benjaluck; Sabmee, Yupa; Singchareon, Ratsamikorn; Slamanig, Stefan; Suthepakul, Nava; Tcheou, Johnstone; Thantamnu, Narumon; Theerasurakarn, Sompone; Tran, Steven; Vilasmongkolchai, Thanakrit; White, Jessica A.; Bhardwaj, Nina; García‐Sastre, Adolfo; Palese, Peter; Krammer, Florian; Poopipatpol, Kittisak; Wirachwong, Ponthip; Hjorth, Richard; Innis, Bruce L.

doi:10.1016/j.eclinm.2022.101323

Cited by 39 publications

(44 citation statements)

References 22 publications

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“…In addition, in this interim analysis, neutralizing activity against variants of concern could not be assessed. Furthermore, we were not able to directly compare immune responses induced by inactivated NDV-vectored SARS-CoV-2 vaccines (41) with those observed following administration of other authorized/licensed COVID-19 vaccines. We expect to perform these additional assays and direct comparisons at later time points as soon as reagents and materials become available.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that an inactivated, as well a live version of this NDV-vectored vaccine, are safe, well tolerated, highly immunogenic and protective in animal models including in a swine model using different routes of administration, that contributed to the design of the phase I protocol reported herein (25)(26)(27)(28)(31)(32)(33). Inactivated versions of the vaccine are currently in clinical development in Vietnam (NCT04830800), Brazil (NCT04993209) and Thailand (NCT04764422).…”

Section: Introductionmentioning

confidence: 99%

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Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico

Ponce-de-León

Torres

Soto-Ramírez

et al. 2022

Preprint

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There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico

Ponce-de-León

Torres

Soto-Ramírez

et al. 2022

Preprint

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“…NDV is being assessed as a vector for a SARS-CoV-2 vaccine (NDV-HXP-S) that is currently in Phase 1/2 clinical trials using an inactivated form of NDV-HXP-S administered intramuscularly, with or without the Toll-like Receptor 9 agonist adjuvant, CpG 1018 [ 79 ]. An interim report of one of the trials found that the vaccine has an acceptable safety profile and is a potent immunogen [ 113 ]. A benefit of this vaccine is that it uses egg-based manufacturing, which could make it suitable for large-scale production if existing influenza vaccine manufacturing capacity is leveraged [ 114 ].…”

Section: Virus Vectors In Developmentmentioning

confidence: 99%

Utilization of Viral Vector Vaccines in Preparing for Future Pandemics

2022

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As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics.

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“…This vaccine is based on an avirulent Newcastle disease virus (NDV) strain which presents a SARS-CoV-2 spike protein stabilized in its prefusion-conformation by the introduction of six proline mutations (HexaPro, HXP-S) [4, 12] and elimination of the furin cleavage site. NDV-HXP-S can be used as live vaccine [11, 13, 14] or as an inactivated vaccine [11, 15]. Clinical trials with a live version are ongoing in Mexico (NCT04871737) and the US (NCT05181709), while the inactivated vaccine is being tested in Vietnam (NCT04830800), Thailand (NCT04764422) and Brazil (NCT04993209).…”

Section: Introductionmentioning

confidence: 99%

“…Clinical trials with a live version are ongoing in Mexico (NCT04871737) and the US (NCT05181709), while the inactivated vaccine is being tested in Vietnam (NCT04830800), Thailand (NCT04764422) and Brazil (NCT04993209). Interim results from the initial Phase I/II trials have demonstrated that the vaccine was safe and immunogenic [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice

Martínez

Slamanig

Lemus

et al. 2022

Preprint

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Equitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant.

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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

Cited by 39 publications

References 22 publications

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico

Utilization of Viral Vector Vaccines in Preparing for Future Pandemics

Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice

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