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SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.
Ober Shepherd, Brittany L; Scott, Paul T; Hutter, Jack N; Lee, Christine; McCauley, Melanie D; Guzman, Ivelese; Bryant, Christopher; McGuire, Sarah; Kennedy, Jessie; Chen, Wei-Hung; Hajduczki, Agnes; Mdluli, Thembi; Valencia-Ruiz, Anais; Amare, Mihret F; Matyas, Gary R; Rao, Mangala; Rolland, Morgane; Mascola, John R; De Rosa, Stephen C; McElrath, M Juliana; Montefiori, David C; Serebryannyy, Leonid; McDermott, Adrian B; Peel, Sheila A; Collins, Natalie D; Joyce, M Gordon; Robb, Merlin L; Michael, Nelson L; Vasan, Sandhya; Modjarrad, Kayvon.
Afiliação
  • Ober Shepherd BL; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Scott PT; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Global Clinical Development, Vaccines, Merck, Rahway, NJ, USA.
  • Hutter JN; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Lee C; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • McCauley MD; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Guzman I; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Bryant C; The Emmes Company, Rockville, MD, USA.
  • McGuire S; The Emmes Company, Rockville, MD, USA.
  • Kennedy J; The Emmes Company, Rockville, MD, USA.
  • Chen WH; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Hajduczki A; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Mdluli T; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Valencia-Ruiz A; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Amare MF; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Matyas GR; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Rao M; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Rolland M; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Departments of Lab Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • McElrath MJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Departments of Lab Medicine and Pathology, University of Washington, Seattle, WA, USA.
  • Montefiori DC; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
  • Serebryannyy L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • McDermott AB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Immunology, Sanofi Vaccines, Lyon, France.
  • Peel SA; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Collins ND; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Joyce MG; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Robb ML; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Michael NL; Walter Reed Army Institute of Research, Silver Spring, MD, USA. Electronic address: nelson.l.michael2.civ@health.mil.
  • Vasan S; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Modjarrad K; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Vaccine Research and Development, Pfizer, Pearl River, NY, USA.
Lancet Microbe ; 5(6): e581-e593, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38761816
ABSTRACT

BACKGROUND:

A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial.

METHODS:

In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (552) to receive 25 µg or 50 µg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181. Enrolment and randomisation occurred sequentially by group; randomisation was done by an interactive web-based randomisation system and only designated unmasked study personnel had access to the randomisation code. Adults were required to be seronegative and unvaccinated for inclusion. Local and systemic reactogenicity, adverse events, binding and neutralising antibodies, and antigen-specific T-cell responses were quantified. For safety analyses, exact 95% Clopper-Pearson CIs for the probability of any incidence of an unsolicited adverse event was computed for each group. For immunogenicity results, CIs for binary variables were computed using the exact Clopper-Pearson methodology, while CIs for geometric mean titres were based on 10 000 empirical bootstrap samples. Post-hoc, paired one-sample t tests were used to assess the increase in mean log-10 neutralising antibody titres between day 29 and day 43 (after the second vaccination) for the primary SARS-CoV-2 targets of interest. This trial is registered at ClinicalTrials.gov, NCT04784767, and is closed to new participants.

FINDINGS:

Between April 7, and June 29, 2021, 29 participants were enrolled in the study. 20 individuals were assigned to receive 25 µg SpFN/ALFQ, four to 50 µg SpFN/ALFQ, and five to placebo. Neutralising antibody responses peaked at day 43, 2 weeks after the second dose. Neutralisation activity against multiple omicron subvariants decayed more slowly than against the D614G or beta variants until 5 months after second vaccination for both dose groups. CD4+ T-cell responses were elicited 4 weeks after the first dose and were boosted after a second dose of SpFN/ALFQ for both dose groups. Neutralising antibody titres against early omicron subvariants and clade 1 sarbecoviruses were detectable after two immunisations and peaked after the third immunisation for both dose groups. Neutralising antibody titres against XBB.1.5 were detected after three vaccinations. Passive IgG transfer from vaccinated volunteers into Syrian golden hamsters controlled replication of SARS-CoV-1 after challenge.

INTERPRETATION:

SpFN/ALFQ was well tolerated and elicited robust and durable binding antibody and neutralising antibody titres against a broad panel of SARS-CoV-2 variants and other sarbecoviruses.

FUNDING:

US Department of Defense, Defense Health Agency.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nanopartículas / Ferritinas / Glicoproteína da Espícula de Coronavírus / Vacinas contra COVID-19 / SARS-CoV-2 / COVID-19 / Lipídeo A / Lipossomos Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nanopartículas / Ferritinas / Glicoproteína da Espícula de Coronavírus / Vacinas contra COVID-19 / SARS-CoV-2 / COVID-19 / Lipídeo A / Lipossomos Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article