Phase 2 Randomized Trial of an AS03 Adjuvanted Plant-Based Virus-Like Particle Vaccine for Covid-19 in Healthy Adults, Older Adults and Adults with Comorbidities

Abstract

The rapid spread of SARS-CoV-2 globally continues to impact humanity on a global scale with rising morbidity and mortality. Despite the development of multiple effective vaccines, new vaccines continue to be required to supply ongoing demand. We report Day 42 interim safety and immunogenicity data from a Phase 2, randomized, placebo-controlled trial in Adults aged 18+ immunized with a virus-like particle vaccine candidate produced in plants displaying SARS-CoV-2 spike glycoprotein (CoVLP) adjuvanted with AS03 (NCT04636697). This report focuses on presenting safety, tolerability and immunogenicity, as measured by neutralizing antibody (NAb) and cell mediated immunity (IFN-γ and IL-4 ELISpot) responses, in Adults aged 18-64 (Adults) and Older Adults aged 65+ (Older Adults). CoVLP adjuvanted with AS03 was well-tolerated and adverse events (AE) were primarily mild or moderate and of transient duration. AEs in Older Adults were more limited than those observed in the Adult population. CoVLP with AS03 induced a significant humoral immune response in both age cohorts. CoVLP with AS03 induced a greater humoral response in Adults than Older Adults after a single dose but this effect was overcome with a second dose when both age cohorts responded with NAb titers that were ~10-fold higher than those in a panel of sera from patients recovering from COVID-19. A single dose of CoVLP with AS03 induced a significant IFN-γ response in both age cohorts; a second dose significantly boosted IFN-γ and IL-4 responses in both age cohorts. Adults generated a stronger IFN-γ and IL-4 cellular response than did Older Adults after one or two doses of AS03-adjuvanted CoVLP. Safety and immunogenicity from Adults with comorbidities as well as final safety and immunogenicity responses after 12 months will be reported upon availability.

Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

“…Vaccination with a single as well as a double dose of CoVLP plus ASO3 induced a significant cellular immune response via interferon gamma (IFN-γ) and IL-4 responses, which was relatively stronger in adults than in the elderly. Consistent with phase 1 trial results, adverse effects were mild to moderate and of a transient duration, such as injection site pain, muscle ache, and fatigue for 24 h to 3 days [50]. The CoVLP vaccine entered the phase 3 portion of the clinical trial on March 16, 2021.…”

“…The interim report on the phase 2 portion of the clinical trial was released on May 18, 2021, reiterating the safety and immunogenicity of the CoVLP vaccine indicated by the phase 1 clinical trial. Double doses of 3.75 µg of CoVLP formulated with ASO3 significantly induced a humoral immune response in both age groups, although the response was greater in adults than in the elderly after a single dose [50]. The level of neutralizing antibodies induced by CoVLP plus ASO3 was 10 times higher than that observed in the convalescent sera of people who recovered from COVID-19.…”

“…In 2012, the program, in collaboration with Medicago, Canada, successfully manufactured 10 million doses of monovalent H1N1 VLP vaccine in tobacco plants within 30 days, accomplishing the proof-of-concept objective to demonstrate the potential scalability and rapidity of plant production to combat the influenza pandemic [41]. Numerous plant-based vaccines against a wide range of pathogens and diseases, including influenza, Ebola, rabies, hepatitis B, norovirus malaria, anthrax, and rotavirus, have entered different phases of clinical trials (Table 2) [27,36,48,50,58,59,62,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Recently, the quadrivalent vaccine developed by Medicago for seasonal influenza has completed a phase 3 clinical trial [48].…”

“…Oral immunization of mice with S1 protein-expressing transgenic tomato induced a high level of SARS-CoV-specific immunoglobulin IgA, while parenteral immunization with tobacco produced S1-induced SARS-CoV-specific IgG in mice [46]. The plant-based recombinant protein production approach has been implemented for the development of vaccines, diagnostic reagents, and therapeutics for COVID-19 and has progressed into clinical trials [48][49][50][51][52][53][54][55][56][57]. The coronavirus virus-like particle (CoVLP) vaccine is in phase 3 and Kentucky Bioprocessing (KBP)-201 in phase 1/2 clinical trials, while IBIO-200, IBIO-201, IBIO-202, Baiya SARS-CoV vax 1, and many more are in the preclinical phase of development (Table 1) [51,[58][59][60].…”

Virus-like particles against infectious disease and cancer: guidance for the nano-architect

“…COVID-19 vaccine candidates have been developed using Tag/Catcher ligation, coupling to the protein nanoparticles mi3 [ 42 ], AP205 [ 48 ] (Trial ID: NCT04839146 ), or HBsAg [ 43 ] (Trial ID: ACTRN12620000817943). Also, VLPs displaying spike trimer, budded from intracellular membranes of Nicotiana benthamiana , entered Phase II/III (Trial ID: NCT04636697 ) [ 49 ].…”