Covifenz (virus-like particles (VLP) of SARS-CoV-2 spike protein) / Mitsubishi Tanabe, Laval University, Dynavax, GSK - LARVOL DELTA

Globally approved vaccines for COVID-19: a systematic review. (PubMed, Braz J Microbiol) - "The vaccines included in this study were: Cominarty, mRNA-1273 or Spikevax, Vaxzevria or AZD1222 or Covishield, CoronaVac or PicoVacc, and Ad26.COV2.S, SputnikV or Gam-Covid-Vac, Covaxin, NVX-CoV2373 or Covovax or Nuvaxovid, WIV04 and HB02, CoVLP or Covifenz and Convidecia or Ad5-nCoV...All vaccines evaluated have different compositions, dosages, populations, and study designs. All are effective in at least preventing symptomatic COVID-19, causing mild or moderate adverse effects when present."

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

MOSAIC: Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity (clinicaltrials.gov) - P2 | N=669 | Active, not recruiting | Sponsor: Canadian Immunization Research Network | Trial completion date: May 2024 ➔ Feb 2025 | Trial primary completion date: Mar 2024 ➔ Nov 2024

Adverse events • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans. (PubMed, Sci Immunol) - "Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response."

Journal • Infectious Disease • Novel Coronavirus Disease • CD4

MOSAIC: Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity (clinicaltrials.gov) - P2 | N=669 | Active, not recruiting | Sponsor: Canadian Immunization Research Network | Trial primary completion date: Oct 2023 ➔ Mar 2024

Adverse events • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Green Biologics: Harnessing the Power of Plants to Produce Pharmaceuticals. (PubMed, Int J Mol Sci) - "Plants have proved that they can produce life-saving therapeutic proteins (Elelyso™-Gaucher's disease treatment, ZMapp™-anti-Ebola monoclonal antibodies, seasonal flu vaccine, Covifenz™-SARS-CoV-2 virus-like particle vaccine); however, some of these therapeutic proteins are difficult to bring to market, which leads to serious difficulties for the manufacturing companies...The versatility of plant-derived biologics across diverse fields, such as human and animal health, industry, and agriculture, is emphasized. This review also meticulously examines regulatory considerations specific to plant-derived biologics, shedding light on the disparities faced compared to biologics produced in other systems."

Journal • Review • Ebola Virus Disease • Gaucher Disease • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

MOSAIC: Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity (clinicaltrials.gov) - P2 | N=669 | Active, not recruiting | Sponsor: Canadian Immunization Research Network | Trial completion date: Sep 2023 ➔ Mar 2024 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Adverse events • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Phase 3 Study to Evaluate the Lot Consistency of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: Medicago | N=900 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease • Novel Coronavirus Disease

Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） (clinicaltrials.gov) - P1/2 | N=128 | Terminated | Sponsor: Medicago | N=296 ➔ 128

Enrollment change • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL4

Plant-made vaccines against viral diseases in humans and farm animals. (PubMed, Front Plant Sci) - "We discuss different production approaches, including stable transgenic plants and transient expression technologies, and review selected applications in the area of human and veterinary vaccines. We also highlight specific challenges associated with viral vaccine production for different target organisms, including lower vertebrates (e.g., farmed fish), and discuss future perspectives for the field."

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

MOSAIC: Mix and Match of the COVID-19 Vaccine for Safety and Immunogenicity (clinicaltrials.gov) - P2 | N=669 | Active, not recruiting | Sponsor: Canadian Immunization Research Network | Recruiting ➔ Active, not recruiting | N=1060 ➔ 669 | Trial completion date: Apr 2023 ➔ Sep 2023

Adverse events • Enrollment change • Enrollment closed • Trial completion date • Infectious Disease • Novel Coronavirus Disease

Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） (clinicaltrials.gov) - P1/2 | N=296 | Terminated | Sponsor: Medicago | And boosters must be dosed after ancestral vaccination approved in Japan. The study was terminated for ethical reason to prioritize the ancestral vaccination.

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

Robust induction of functional humoral response by a plant-derived Coronavirus-like particle vaccine candidate for COVID-19. (PubMed, NPJ Vaccines) - "AS03-adjuvanted CoVLP induced robust and durable SARS-CoV-2 specific humoral immunity, marked by strong IgG1antibody responses, potent FcγR binding, and antibody effector function. Contrary to a decline in neutralizing antibody titers, the FcγR2A-receptor binding capacity and antibody-mediated effector functions, such as opsonophagocytosis, remained readily detectable for at least six months."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of an AS03-adjuvanted plant-based SARS-CoV-2 vaccine in Adults with and without Comorbidities. (PubMed, NPJ Vaccines) - P2/3 | "A Th1-biased response was most evident after the first dose and was still present after the second dose. These data demonstrated that CoVLP+AS03 is well-tolerated and highly immunogenic, generating a durable (at least 6 months) immune response against different VOCs, in adults ≥18 years of age, with and without comorbidities."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG • IL4

Durability and cross-reactivity of immune responses induced by a plant-based virus-like particle vaccine for COVID-19. (PubMed, Nat Commun) - P1 | "Results are similar with the pseudovirion assay. These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG • IL4

Broad neutralization against SARS-CoV-2 variants induced by ancestral and B.1.351 AS03-Adjuvanted recombinant Plant-Derived Virus-Like particle vaccines. (PubMed, Vaccine) - "A recombinant plant-derived virus-like particle vaccine for the ancestral COVID-19 (CoVLP) recently authorized by Canadian Health Authorities and a modified CoVLP.B1351 targeting the B.1.351 variant (both formulated with the adjuvant AS03) were assessed in homologous and heterologous prime-boost regimen in mice. Both strategies induced strong and broadly cross-reactive neutralizing antibody (NAb) responses against several Variants of Concern (VOCs), including B.1.351/Beta, B.1.1.7/Alpha, P.1/Gamma, B.1.617.2/Delta and B.1.1.529/Omicron strains. The neutralizing antibody (NAb) response was robust with both primary vaccination strategies and tended to be higher for almost all VOCs following the heterologous prime-boost regimen."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

What is the future of Covid-19 pharmaceuticals? (Royal Society of Chemistry) - "'All policy makers cared about was speed and innovation,' says Peter Hotez...'They got what they paid for: interesting vaccines for smaller populations in the northern hemisphere.' Early vaccine shipments went to those willing to pay top dollar. But leaving parts of the world unvaccinated has proven risky. Hotez points to the delta and omicron variants both coming out of unvaccinated populations in India and southern Africa, respectively."

Media quote • Novel Coronavirus Disease

Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine. (PubMed, N Engl J Med) - P2/3 | "The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.)."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety, Tolerability and Immunogenicinity of a Coronavirus-Like Particle COVID-19 Vaccine in Adults Aged 18-55 Years. (clinicaltrials.gov) - P1 | N=180 | Completed | Sponsor: Medicago | Active, not recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Aug 2021

Trial completion • Trial completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG • IL4

Study of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine in Adults (clinicaltrials.gov) - P2/3 | N=30918 | Active, not recruiting | Sponsor: Medicago | Trial primary completion date: Dec 2021 ➔ Aug 2021

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

Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） (clinicaltrials.gov) - P1/2 | N=296 | Active, not recruiting | Sponsor: Medicago | N=145 ➔ 296

Enrollment change • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） (clinicaltrials.gov) - P1/2 | N=145 | Active, not recruiting | Sponsor: Medicago | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2021 ➔ Mar 2022

Enrollment closed • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates. (PubMed, Cell Mol Immunol) - "No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4 • IL2 • IL4

Lack of Effects on Female Fertility or Pre- and Postnatal Development of Offspring in Rats after Exposure to AS03-adjuvanted Recombinant Plant-Derived Virus-Like Particle Vaccine Candidate for COVID-19. (PubMed, Reprod Toxicol) - "There was no evidence of untoward effects on embryo-fetal development (including teratogenicity), or early (pre-weaning) development of the F1 offspring. These results support the acceptable safety profile of the AS03-adjuvanted CoVLP vaccine for administration to women of childbearing potential."

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

Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） (clinicaltrials.gov) - P1/2; N=145; Recruiting; Sponsor: Medicago; Enrolling by invitation ➔ Recruiting

Clinical • Enrollment status • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

Safety Immunogenicity Study of MT-2766 in Japanese Adults（COVID-19） (clinicaltrials.gov) - P1/2; N=145; Enrolling by invitation; Sponsor: Medicago; Recruiting ➔ Enrolling by invitation

Clinical • Enrollment status • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG