Safety and immunogenicity of a SARS-CoV-2 Gamma variant RBD-based protein adjuvanted vaccine used as booster in healthy adults

Abstract

A Gamma Variant RBD-based aluminum hydroxide adjuvanted vaccine called ARVAC CG was selected for a first in human clinical trial. Healthy male and female participants (18-55 years old) with a complete COVID-19-primary vaccine scheme were assigned to receive two intramuscular doses of either a low-dose or a high-dose of ARVAC CG. The primary endpoint was safety. The secondary objective was humoral immunogenicity. Cellular immune responses were studied as an exploratory objective. The trial was prospectively registered in PRIISA.BA (Registration Code 6564) and ANMAT and retrospectively registered in ClinicalTrials.gov (NCT05656508). Samples from participants of a surveillance strategy implemented by the Ministry of Health of the Province of Buenos Aires that were boosted with BNT162b2 were also analyzed to compare with the booster effect of ARVAC CG. ARVAC CG exhibits a satisfactory safety profile, a robust and broad booster response of neutralizing antibodies against the Ancestral strain of SARS-CoV-2 and the Gamma, Delta, Omicron BA.1 and Omicron BA.5 variants of concern and a booster effect on T cell immunity in individuals previously immunized with different COVID-19 vaccine platforms.

Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster

“…Several RBD protein vaccines are now in various stages of development or implementation, 25 and selected candidates in late-stage clinical trials or licensure are summarised in Table 2 . 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 Of particular interest are: (1) A dimeric RBD vaccine (ZF2001) where two RBD subunits are linked via an engineered single-chain construct, adjuvanted with alum, approved for emergency use in China and some other countries. This was tested as a three-dose schedule 28 ; (2) Cuba has developed a series of RBD-based vaccines including Soberana-02 (RBD conjugated to tetanus toxoid) and a dimeric RBD vaccine to be used as a booster (Soberana-Plus), both adjuvanted with Alum.…”

“… Alum hydroxide 3 HIPRA. PHH-1V 36 CHO RBD fusion heterodimer incorporating alpha and beta variant RBDs SQBA (Squalene-based oil-in-water) 1/2a Laboratorio Pablo Cassará ARVAC CG 37 CHO Single chain dimer of gamma variant RBD Alum hydroxide 1 Radboud University, NL. ABNCoV2 38 Schneider-2 (ExpreS2) cells RBD-coated capsid virus-like particle MF59 in a subgroup 1 LLC Betuvax Betuvax-CoV-2 39 CHO RBD-Fc dimer assembled as Betuspheres (betulin nanoparticles) Betulin (triterpenoid of lupane structure) 1/2 Walvax/Abogen ARC0V-mRNA (AWcorna) 40 mRNA RBD mRNA encapsulated in Abogen proprietary LNP N/A 3, emerg licence Indonesia (Sept 2022) All but three are targeted at ancestral strain RBD—a beta variant version of the V-01 vaccine that was tested in a pilot study, the HIPRA candidate has a beta RBD target (as alpha/beta heterodimer), and ARVAC CG uses the gamma variant RBD.…”

Safe plant Hsp90 adjuvants elicit an effective immune response against SARS-CoV2 derived RBD antigen

“…Although previous studies carried out on vaccines against Ebola or Mers-CoV have contributed to laying the foundations for vaccine development in pandemic situations [28], the pandemic experience with SARS-CoV2 consolidated the concept of rapid approval of vaccines through the intervention of international organizations such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for health emergencies [29]. In fact, a vaccine against SARS-CoV2 named ArVac-CG, based on a recombinant RBD antigen, was recently approved in Argentina [30]. Although this establishes solid foundations for future pandemic experiences that could take place in Argentina, emerging and socially and economically vulnerable countries remain at a disadvantage if new pandemic situations happen again.…”

“…ArVac-CG (319R, 537K) [30] or (R328, T531) [22]. All of these were effective in eliciting a protective immune response.…”

“…As far as we know, the RBD protein (V401; F541) analyzed in this work is a shorter version than others previously studied. Mainly, it is smaller in the N-terminal region than several of those already used, such as NARUVAX-C19 (Q321, S521)[38], ArVac-CG (319R, 537K)[30] or (R328, T531)[22]. All of these were effective in eliciting a protective immune response.…”