Butanvac (Coronavirus Vaccine) / Oswaldo Cruz Foundation, Butantan Institute - LARVOL DELTA

One year follow up of phase 1/2 randomized, placebo controlled trial of NDV-HXP-S vaccine in Thailand. (PubMed, NPJ Vaccines) - "The two-dose NDV-HPX-S primary series was safe and elicited a strong immune response over one year, especially in the 3 µg+CpG and 10 µg groups. The 3 µg+CpG group had a significantly higher geometric mean fold rise (GMFR) than the 3 µg group (57.1 vs 40.0, p = 0.028) 14 days after the second dose."

Clinical • Journal • P1/2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development of an RT-qPCR and a Next-Generation Sequencing approach to assess viral shedding of NDV-based SARS-CoV-2 variant vaccines. (PubMed, Microbiol Spectr) - "Previously, we have developed a Newcastle disease virus (NDV)-based vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named NDV-HXP-S...In this work, we have developed a combined reverse transcriptase-quantitative polymerase chain reaction and next-generation sequencing-directed approach to assess the viral shedding of multivalent Newcastle disease virus-based severe acute respiratory syndrome coronavirus 2 vaccines. This new formulation will be evaluated as a mucosal booster in phase I clinical trials next year."

Biomarker • Journal • Next-generation sequencing • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Immunogenicity and efficacy of homologous and heterologous NDV and MVA SARS-CoV-2 vaccines in mice and hamsters. (PubMed, NPJ Vaccines) - "Hamsters vaccinated with NDV-HXP-S exhibited protection of the upper respiratory tract, with the NDV-HXP-S/MVA-S(3P) regimen showing a trend toward reduced direct contact transmission of SARS-CoV-2. These findings demonstrate the capacity of NDV and MVA vector platforms to induce robust systemic and mucosal antigen-specific humoral and T-cell responses against SARS-CoV-2, contributing to protection against both disease and transmission, and support further exploration of these vector platforms for vaccination against SARS-CoV-2 and potentially other pathogens."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD8

Safety and Tolerability of a Newcastle Disease Virus-Based Mucosal COVID-19 Vaccine in Previously Vaccinated Adults (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: CastleVax Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

Safety and Tolerability of a Newcastle Disease Virus-Based Mucosal COVID-19 Vaccine in Previously Vaccinated Adults (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: CastleVax Inc.

New P2 trial • Infectious Disease • Novel Coronavirus Disease

Development of a next-generation COVID-19 intranasal vaccine based on a multivalent NDV-HXP-S formulation. (ESWI 2025) - No abstract available

Infectious Disease • Novel Coronavirus Disease

Immune responses to a heterologous booster with mRNA based COVID-19 vaccine after priming with an inactivated Newcastle disease virus recombinant vaccine expressing the SARS-CoV-2 spike protein (NDV-HXP-S). (PubMed, Vaccine) - "The immune responses stimulated by the heterologous boost with bivalent mRNA vaccine in the NDV-HXP-S primed groups were high especially among the hybrid immune subgroup. Thai Clinical Trial Registry: WHO REGISTRY PLATFORM- TCTR20230809003."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

A Live Recombinant Newcastle Disease Virus-vectored COVID-19 Vaccine Phase 1 Study. (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Sean Liu | Active, not recruiting ➔ Completed | Trial completion date: Nov 2025 ➔ Apr 2024

Trial completion • Trial completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Mucosal multivalent NDV-based vaccine provides cross-reactive immune responses against SARS-CoV-2 variants in animal models. (PubMed, Front Immunol) - "Furthermore, intranasal trivalent live NDV-HXP-S boosted systemic and mucosal immunity in mice pre-immunized with mRNA vaccine. Overall, a mucosal multivalent live NDV-HXP-S vaccine shows great promise as a safe, next-generation vaccine conferring broad mucosal and systemic immunity against future SARS-CoV-2 variants."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Results of a randomized vaccine-controlled phase I ADAPTCOV trial in Brazil. (PubMed, Vaccine) - P1 | "This is a single-center, randomized, double-blind, active-controlled dose-escalating phase I clinical trial to evaluate the immunogenicity and safety of NDV-HXP-S (1 μg, 3 μg, and 10 μg), an inactivated COVID-19 vectored-vaccine virus using the Newcastle Disease Virus (NDV) expressing stabilized pre-fusion S protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)...The vaccine also displayed a very favorable safety profile. ClinicalTrials.gov,NCT04993209."

Clinical • Journal • P1 data • Fatigue • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

Phase II/III Randomized Clinical Trial of Booster Dose of COVID-19 (Recombinant, Inactivated) Vaccine (clinicaltrials.gov) - P2/3 | N=4400 | Completed | Sponsor: Butantan Institute | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A single immunization with intranasal Newcastle disease virus (NDV)-based XBB.1.5 variant vaccine reduces disease and transmission in animals against matched-variant challenge. (PubMed, Vaccine) - "Furthermore, one or two intranasal vaccinations with NDV-HXP-S XBB.1.5 protected hamsters from variant matched infection and reduced virus emission, thereby providing complete protection to naïve animals in a direct contact transmission study. The data shown in this study supports the notion that intranasal vaccination with variant-adapted NDV-HXP-S induces protective mucosal immunity and reduces transmission rates, highlighting the robust protective efficacy of a single mucosal vaccination in mice and hamsters."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: A randomised, comparator-controlled, phase 2 trial. (PubMed, Vaccine) - "NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Considering that induction of neutralising antibodies against SARS-CoV-2 has been correlated with the efficacy of COVID-19 vaccines, including VAXZEVRIA, our results suggest that vaccination with COVIVAC may afford clinical benefit matching or exceeding that of the VAXZEVRIA vaccine. ClinicalTrials.govNCT05940194."

Journal • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Live Recombinant Newcastle Disease Virus-vectored COVID-19 Vaccine Phase 1 Study. (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Sean Liu | Trial completion date: Apr 2024 ➔ Nov 2025

Trial completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development of multidose thermotolerant formulations of a vector-based Covid-19 vaccine candidate, NDV-HXP-S in different product formats: Stability and preservative efficacy study. (PubMed, Vaccine X) - "Lead lyophilized vaccine formulations were identified which were able to maintain S-antigen content for six months at 2 °C to 8 °C, 25 °C, and 40 °C. Both the liquid and lyophilized formulations identified are improved thermotolerant SARS-CoV-2 vaccine formulations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Intranasal SARS-CoV-2 Omicron variant vaccines elicit humoral and cellular mucosal immunity in female mice. (PubMed, EBioMedicine) - "We demonstrate that NDV-HXP-S Omicron variant vaccines utilised for primary immunizations or boosting efficiently elicit humoral and cellular immunity. The described induction of systemic and mucosal immunity has the potential to reduce infection and transmission."

Journal • Preclinical • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

A Live Recombinant Newcastle Disease Virus-vectored COVID-19 Vaccine Phase 1 Study. (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: Sean Liu | Trial primary completion date: Apr 2024 ➔ May 2023

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development of a quantitative ELISA for SARS-CoV-2 vaccine candidate, NDV-HXP-S, with CpG 1018® adjuvant. (PubMed, Hum Vaccin Immunother) - "The vaccine was mixed with and without CpG 1018® adjuvant in saline and maintained S-antigen content at 2°C to 8°C for the entire 6-month period. Additionally, a pilot controlled temperature chain (CTC) stability study was conducted at the completion of the 6-month study and demonstrated the possibility for this vaccine candidate to attain CTC stability labeling."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of homologous or heterologous vaccine booster over two initial doses of inactivated COVID-19 vaccine. (PubMed, Expert Rev Vaccines) - "Immune responses generated after one dose of heterologous boost were high and able to preventing severity of disease and symptomatic infection. New approach of inactivated vaccine has been developed using inactivating recombinant vector virus-NDV-HXP-S vaccine."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

NDV-HXP-S, a COVID-19 vaccine to boost mucosal immunity. (ESWI 2023) - No abstract available

Late-breaking abstract • Infectious Disease • Novel Coronavirus Disease

Trivalent NDV-HXP-S Vaccine Protects against Phylogenetically Distant SARS-CoV-2 Variants of Concern in Mice (ESWI 2023) - No abstract available

Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Phase II/III Randomized Clinical Trial of Booster Dose of COVID-19 (Recombinant, Inactivated) Vaccine (clinicaltrials.gov) - P2/3 | N=4400 | Active, not recruiting | Sponsor: Butantan Institute | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2024 ➔ Sep 2024

Enrollment closed • Trial completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Solid Tumor

ADAPTCOV: Clinical Trial of the COVID-19 Vaccine (Recombinant, Inactivated) in Brazil (clinicaltrials.gov) - P1 | N=320 | Completed | Sponsor: Butantan Institute | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

NDV-HXP-S Vaccine Clinical Trial (COVIVAC) (clinicaltrials.gov) - P2 | N=374 | Completed | Sponsor: Institute of Vaccines and Medical Biologicals, Vietnam

New P2 trial • Infectious Disease • Novel Coronavirus Disease

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico. (PubMed, NPJ Vaccines) - P1 | "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)...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."

Journal • P1 data • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases