SARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine / Walter Reed Army Institute of Research, USAMRIID - LARVOL DELTA

Production of Clinical-Grade SARS-CoV-2 Spike Ferritin Nanoparticle Protein Immunogen by Transient Transfection. (PubMed, Vaccines (Basel)) - "SpFN material produced using the CGMP protocols adjuvanted with Army Liposomal Formulation-QS-21 (ALFQ) elicited potent neutralizing antibodies against WA-1, Alpha, Beta, and Delta variants in mice as measured by a pseudovirus neutralization assay. This work demonstrates rapid development and scaled-up production of clinical-grade SARS-CoV-2 vaccine protein material, allowing permissive storage and transport conditions, and serves as a framework for recombinant protein production for future emergent pathogens."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

PHASE 1 SARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine With ALFQ Adjuvant for Prevention of COVID-19 (clinicaltrials.gov) - P1 | N=29 | Completed | Sponsor: U.S. Army Medical Research and Development Command | Active, not recruiting ➔ Completed

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

SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity. (PubMed, iScience) - "We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity...Purified equine polyclonal IgG provided protection against Omicron XBB.1.5 virus in the K18-hACE2 transgenic mouse model. These results suggest that SARS-CoV-2-based nanoparticle vaccines can rapidly produce a broad and protective sarbecovirus response in the equine model and that equine serum has therapeutic potential against emerging SARS-CoV-2 VoC and diverse sarbecoviruses, presenting a possible alternative or supplement to monoclonal antibody immunotherapies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

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. (PubMed, Lancet Microbe) - P1 | "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."

Journal • P1 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

First-in-Human Phase I Trial of an Adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine (CROI 2024) - "Individuals vaccinated with SpFN/ALFQ mounted neutralizing antibody responses against multiple clade 1 sarbecoviruses. The results of this first-in-human clinical trial represents a platform upon which to build future sarbecovirus vaccine development."

Clinical • P1 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques. (PubMed, Nat Commun) - "Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates...In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

IgG Antibodies from humans vaccinated with a SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21 are protective in Syrian golden hamsters (ASTMH 2023) - P1 | "Qualitative weight loss and a significant reduction in viral loads was observed in the lower airways within 6 days after the challenge. While larger studies are needed, these results build upon the hypothesis that Spike-specific BAb and NAb from Sp FN/ALFQ vaccinated humans have protective capacity against clade 1 sarbecoviruses."

Clinical • Late-breaking abstract • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ad26.COV2.S and SARS-CoV-2 spike protein ferritin nanoparticle vaccine protect against SARS-CoV-2 Omicron BA.5 challenge in macaques. (PubMed, Cell Rep Med) - "All three regimens suppress peak and day 4 viral loads in the respiratory tract, which correlate with both humoral and cellular immune responses. This study demonstrates that both homologous and heterologous regimens involving Ad26.COV2.S and SpFN vaccines provide robust protection against a mismatched BA.5 challenge in macaques."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4 • CD8

SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies. (PubMed, NPJ Vaccines) - "These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL21

A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model. (PubMed, Vaccines (Basel)) - "The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization."

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

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity. (PubMed, Cell Rep) - "A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses. (PubMed, NPJ Vaccines) - "We assessed a SARS-CoV-2 spike-ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel or Army Liposome Formulation containing QS-21 (ALFQ) for unique vaccine evoked immune signatures...The presence of this epitope in SARS-CoV, suggests that generation of cross-reactive T cells may be induced against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant that effectively engages innate immune cells, enhances SARS-CoV-2-specific durable adaptive immune T cell responses."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4 • CD8

A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge. (PubMed, NPJ Vaccines) - "Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine."

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

[VIRTUAL] SARS-CoV-2 Ferritin Nanoparticle Vaccines Elicit Broad SARS Coronavirus Immunogenicity (IDWeek 2021) - "A Spike-Ferritin nanoparticle (SpFN) vaccine elicited neutralizing ID50 titers >10,000 after a single immunization, while RBD-Ferritin (RFN) nanoparticle immunogens elicited ID50 titer values >10,000 values after two immunizations... These observations highlight the importance of SARS-CoV-2 neutralizing antibody levels in providing protection against emerging SARS-like coronaviruses and provide a robust platform for pandemic preparedness. Structure-based design enables development of a SARS-CoV-2 nanoparticle immunogen."

Infectious Disease • Novel Coronavirus Disease

SARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine With ALFQ Adjuvant for Prevention of COVID-19 in Healthy Adults (clinicaltrials.gov) - P1; N=29; Active, not recruiting; Sponsor: U.S. Army Medical Research and Development Command; Recruiting ➔ Active, not recruiting; N=72 ➔ 29

Clinical • Enrollment change • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine With ALFQ Adjuvant for Prevention of COVID-19 in Healthy Adults (clinicaltrials.gov) - P1; N=72; Recruiting; Sponsor: U.S. Army Medical Research and Development Command; Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine With ALFQ Adjuvant for Prevention of COVID-19 in Healthy Adults (clinicaltrials.gov) - P1; N=72; Not yet recruiting; Sponsor: U.S. Army Medical Research and Development Command

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sarepta Therapeutics Announces Research Agreement with U.S. Department of Defense to Evaluate Multiple Constructs From its Proprietary RNA Platform as Treatments for COVID-19 (GlobeNewswire, Sarepta Therapeutics, Inc.) - "Sarepta Therapeutics, Inc....today announced that the Company and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID)...have entered into a Cooperative Research and Development Agreement (CRADA)....Sarepta will design, synthesize, manufacture and provide to USAMRIID multiple peptide-conjugated PMO (PPMO) constructs....USAMRIID will evaluate the constructs on characterized wild-type SARS-CoV-2 viruses for their potential to inhibit viral infection. Based on the results, Sarepta and USAMRIID will consider collaborative funding proposals to advance the development of treatments for COVID-19."

Licensing / partnership • Infectious Disease • Novel Coronavirus Disease