RTS,S/AS02 is a recombinant protein malaria vaccine that contains a large portion of the C-terminal of the circumsporozoite protein (CSP) sequence of the NF54 isolate of Plasmodium falciparum fused to the hepatitis B virus surface antigen.
RTS,S formulated in AS02A (a GSK proprietary formulation) is the only vaccine candidate shown in field trials to prevent malaria and, in one instance, to limit disease severity.
We wished to extend the analysis to the Pfcsp gene, coding for the dominant sporozoite surface antigen on which the leading malaria vaccine candidate RTS,S is based.
The RTS,S/AS02A vaccine offers significant partial efficacy against malaria.mRNA expression of five key cytokines interferon-gamma (IFN-γ), monokine induced by gamma (MIG), interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and forkhead box P3 (FoxP3) in peripheral blood mononuclear cells were measured by real-time RT-PCR before and after vaccination with RTS,S/AS02A and Modified Vaccinia virus Ankara encoding the circumsporozoite protein (MVA-CS) in healthy malaria-naïve adult volunteers.
The identification of malaria parasite antigens focused efforts on the development of subunit vaccines but has so far yielded only one partially efficacious vaccine candidate, RTS/S.
Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated sporozoites (RAS) have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach.
Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission.
These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria.
This review focuses on product development efforts over the last five years of RTS,S, a pre-erythrocytic, recombinant subunit, adjuvanted, candidate malaria vaccine designed with this goal of a first-generation malaria vaccine in mind.
Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease.
Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite.
Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy.
With demonstration purpose, we apply the software to 30 cytokines, chemokines and growth factors measured in a multiplex bead-based immunoassay in a study aiming to measure correlates of risk or protection from malaria of the RTS,S malaria vaccine nested in the Phase 3 randomized controlled trial of this vaccine.
This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01.
Recent experience with Seasonal Malaria Chemoprevention and with the RTS,S/AS01 malaria vaccine provides examples of interventions which need to be deployed on a restricted rather than a national basis, taking account of differences in climate and the intensity of malaria infection between regions within a country.
IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03).