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Hum Vaccin Immunother
. 2026 Dec;22(1):2689794.
doi: 10.1080/21645515.2026.2689794. Epub 2026 Jul 2.
Safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike and quadrivalent influenza hemagglutinin with Matrix-M® adjuvant: A phase 1/2 clinical trial
Vivek Shinde 1 , Wayne Woo 1 , Anthony M Marchese 1 , Susan Neal 1 , Joyce S Plested 1 , Timothy S Vincent 1 , Mingzhu Zhu 1 , Shane Cloney-Clark 1 , Iksung Cho 1 , Louis Fries 1 , Raburn M Mallory 1 , Gregory M Glenn 1
Affiliations
Based on viral evolution, increases in seasonal infections, and facilitation of delivery, an annual combination vaccine simultaneously targeting influenza and SARS-CoV-2 would benefit public health. The safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike (rS) to the ancestral strain (Wuhan) and quadrivalent influenza hemagglutinin with a Matrix-M® saponin-based adjuvant were evaluated in a phase 1/2 blinded, randomized trial. The safety, tolerability, and immunogenicity of a CIC two-dose series were assessed and compared with standalone quadrivalent influenza (qNIV) and monovalent COVID-19 (NVX-CoV2373) vaccines. Reactogenicity events, unsolicited adverse events (AEs), antiviral microneutralization responses, hemagglutination-inhibition antibody titers, anti-rS protein immunoglobulin G, and human angiotensin-converting enzyme 2 receptor binding inhibition antibody responses for SARS-CoV-2 were measured. All participants had been previously vaccinated against ancestral SARS-CoV-2. From September 8, 2021, to April 22, 2022, 642 participants were enrolled and randomized into the study; 637 received at least one vaccination. After each dose, CIC formulations induced antibody responses against homologous and heterologous influenza and SARS-CoV-2 strains that were comparable with the references. The CIC vaccine group had similar incidence of solicited and unsolicited AEs as the qNIV and NVX-CoV2373 reference groups. Severe unsolicited AEs only occurred in the CIC group but were infrequent and not considered related to the study vaccine. Overall, CIC formulations displayed reference-comparable safety and immunogenicity and provided data for statistical modeling analyses to optimize influenza hemagglutinin and SARS-CoV-2 rS antigen concentrations for use in phase 2 clinical trials investigating CIC.
Keywords: COVID-19; Matrix-M adjuvant; combination vaccine; immunogenicity; influenza; safety.
. 2026 Dec;22(1):2689794.
doi: 10.1080/21645515.2026.2689794. Epub 2026 Jul 2.
Safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike and quadrivalent influenza hemagglutinin with Matrix-M® adjuvant: A phase 1/2 clinical trial
Vivek Shinde 1 , Wayne Woo 1 , Anthony M Marchese 1 , Susan Neal 1 , Joyce S Plested 1 , Timothy S Vincent 1 , Mingzhu Zhu 1 , Shane Cloney-Clark 1 , Iksung Cho 1 , Louis Fries 1 , Raburn M Mallory 1 , Gregory M Glenn 1
Affiliations
- PMID: 42390526
- DOI: 10.1080/21645515.2026.2689794
Based on viral evolution, increases in seasonal infections, and facilitation of delivery, an annual combination vaccine simultaneously targeting influenza and SARS-CoV-2 would benefit public health. The safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike (rS) to the ancestral strain (Wuhan) and quadrivalent influenza hemagglutinin with a Matrix-M® saponin-based adjuvant were evaluated in a phase 1/2 blinded, randomized trial. The safety, tolerability, and immunogenicity of a CIC two-dose series were assessed and compared with standalone quadrivalent influenza (qNIV) and monovalent COVID-19 (NVX-CoV2373) vaccines. Reactogenicity events, unsolicited adverse events (AEs), antiviral microneutralization responses, hemagglutination-inhibition antibody titers, anti-rS protein immunoglobulin G, and human angiotensin-converting enzyme 2 receptor binding inhibition antibody responses for SARS-CoV-2 were measured. All participants had been previously vaccinated against ancestral SARS-CoV-2. From September 8, 2021, to April 22, 2022, 642 participants were enrolled and randomized into the study; 637 received at least one vaccination. After each dose, CIC formulations induced antibody responses against homologous and heterologous influenza and SARS-CoV-2 strains that were comparable with the references. The CIC vaccine group had similar incidence of solicited and unsolicited AEs as the qNIV and NVX-CoV2373 reference groups. Severe unsolicited AEs only occurred in the CIC group but were infrequent and not considered related to the study vaccine. Overall, CIC formulations displayed reference-comparable safety and immunogenicity and provided data for statistical modeling analyses to optimize influenza hemagglutinin and SARS-CoV-2 rS antigen concentrations for use in phase 2 clinical trials investigating CIC.
Keywords: COVID-19; Matrix-M adjuvant; combination vaccine; immunogenicity; influenza; safety.