Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion InactivatedSARS-CoV-2 Vaccine - BBV152

ABSTRACTWe report the development and evaluation of safety and immunogenicity of a whole virion inactivated SARS-COV-2 vaccine (BBV152), adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established vero cell platform to produce large-scale GMP grade highly purified inactivated antigen, BBV152. Product development and manufacturing were carried out in a BSL-3 facility. Immunogenicity was determined at two antigen concentrations (3μg and 6μg), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-γ+ CD4 T lymphocyte response. Our results support further development for Phase I/II clinical trials in humans.

OC 8546 SAFETY AND IMMUNOGENICITY OF THE MALARIA VACCINE CANDIDATE BK-SE36 IN YOUNG CHILDREN LIVING IN BURKINA FASO

BackgroundThe malaria blood stage vaccine candidate SE-36 is based on the serine repeat antigen of Plasmodium falciparum. Epidemiological studies have shown that antibodies against SE36 correlate with lower parasitaemia in Solomon Island residents. In a phase I b trial conducted in Uganda, the BK-SE36 vaccine, SE36 formulated with aluminium hydroxide gel, was found safe and immunogenic. Interestingly, highest levels of IgG anti-SE36 protein associated with protection against severe malaria were found in the youngest Ugandan trial participants.ObjectivesTo assess the safety and immunogenicity of the BK-SE36 vaccine in a randomised controlled double-blind age de-escalating phase Ib clinical trial in younger (≤5 years) malaria-exposed children living in Burkina Faso.MethodsHealthy participants (108) were included in two age cohorts, one consisting of 54 children aged 25–60 months and the other of 54 children aged 12–24 months. Trial participants received 3 intramuscular or subcutaneous injections of the BK-SE36 vaccine at Day 0, Week 4 and 26. Participants allocated to the control group received the control Synflorix vaccine via intramuscular route at Day 0 and Week 26 and saline at Week 4. The participants were followed for one year. Immune responses were evaluated by ELISA, ELISpot and parasite carriage by microscopy and PCR.ResultsPreliminary data from an interim analysis (data collected one month after the last immunisation) indicated that the vaccine was safe, well-tolerated and induced an IgG anti-SE36 response in these younger populations. The trial’s latest safety, immunogenicity and preliminary efficacy results will be presented.

RECOMBINANT ANTIGENS OF PSEUDOMONAS AERUGINOSA: EFFECT ON IMMUNE RESPONSE IN MICE

Aim. Study the effect of recombinant antigens of P. aeruginosa on key effectors of the immune system. Materials and methods. Mice were immunized intraperiotoneally with 25 jig of OprF and 50 jig of anatoxin sorbed on aluminium hydroxide gel with a 2 week interval. 7 days after the last immunization spleen lymphocyte subpopulation structure was evaluated by flow cytometry. Cytokine levels in mice sera were studied after a single immunization with recombinant OprF and anatoxin at 4, 8, 24 hours and 14 days by flow cytometry using FlowCytomix Mouse Thl/Th2 10 plex. Results. OprF recombinant antigens and anatoxin affect molecular-cell mechanisms of immune response resulting in alteration of expression of differentiating and activating molecules as well as synthesis of Thl/Th2/Thl7/Th21/Th22 cytokines in mice that are necessary for effective presentation of the antigen. Conclusion. Complex of recombinant OprF and anatoxin facilitated formation of complete immune response against pseudomonas.

Evaluation of different adjuvants for foot-and-mouth disease vaccine containing all the SAT serotypes

Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals that is primarily controlled by vaccination of susceptible animals and movement restrictions for animals and animal-derived products in South Africa. Vaccination using aluminium hydroxide gel-saponin (AS) adjuvanted vaccines containing the South African Territories (SAT) serotypes has been shown to be effective both in ensuring that disease does not spread from the endemic to the free zone and in controlling outbreaks in the free zone. Various vaccine formulations containing antigens derived from the SAT serotypes were tested in cattle that were challenged 1 year later. Both the AS and ISA 206B vaccines adjuvanted with saponin protected cattle against virulent virus challenge. The oilbased ISA 206B-adjuvanted vaccine with and without stimulators was evaluated in a field trial and both elicited antibody responses that lasted for 1 year. Furthermore, the ISA 206 adjuvanted FMD vaccine protected groups of cattle against homologous virus challenge at very low payloads, while pigs vaccinated with an emergency ISA 206B-based FMD vaccine containing the SAT 1 vaccine strains were protected against the heterologous SAT 1 outbreak strain.