Abstract
BackgroundIndian-origin rhesus (InR) are preferred for research, but strict export restrictions continue to limit their use. Chinese-origin rhesus (ChR), although easier to procure, are genetically distinct from InR and differ in their immune response to infectious agents, such as the Simian Immunodeficiency Virus. The most advanced malaria vaccine, RTS,S (GlaxoSmithKline), is based on the circumsporozoite protein (CSP) of Plasmodium falciparum. The efficacy of RTS,S vaccine in the field remains low and short-lived; efforts are underway to improve CSP-based vaccines. Rhesus models can accelerate preclinical down-selection of the next generation of malaria vaccines. This study was used to determine if the safety and immunogenicity outcomes following vaccination with a CSP vaccine would differ in the InR and ChR models, given the genetic differences between the two sub-populations of rhesus.MethodsThe FMP013 vaccine, was composed of nearly full-length soluble P. falciparum CSP produced in Escherichia coli and was adjuvanted with the Army liposomal formulation (ALFQ). Three doses of the vaccine were administered in InR and ChR (n = 6) at 1-month intervals and the antibody and T cell responses were assessed.ResultsLocal and systemic toxicity profile of FMP013 vaccine in InR and ChR were similar and they revealed that the FMP013 vaccine was safe and caused only mild and transient inflammatory adverse reactions. Following the first 2 vaccines, there was a slower acquisition of antibodies to the CSP repeat region in ChR. However after the 3rd vaccination the titers in the two models were comparable. The ChR group repeat-specific antibodies had higher avidity and ChR group showed higher inhibition of liver stage development activity compared to InR. There was no difference in T-cell responses to the FMP013 vaccine between the two models.ConclusionsA difference in the quality of serological responses was detected between the two sub-populations of rhesus. However, both models confirmed that FMP013/ALFQ vaccine was safe, highly immunogenic, elicited functional antibodies and T-cell responses. Overall, the data suggests that rhesus of Indian and Chinese origins can be interchangeably used to compare the safety and immunogenicity of next-generation of malaria vaccines and adjuvants.
Highlights
Indian-origin rhesus (InR) are preferred for research, but strict export restrictions continue to limit their use
Local reactogenicity There was no sub-population specific difference between the InR and Chinese-origin rhesus (ChR) with respect to the systemic and local reactions to the falciparum malaria protein-013 com‐ prising of CSP (FMP013) formulated in Army Liposomal Formulation containing QS-21 (ALFQ)
There were no signs of ulcers or abscesses and only minimal, skin warmth, erythema and muscle indurations were caused by three doses of FMP013 vaccine in InR or ChR (Fig. 1a, c, d)
Summary
Indian-origin rhesus (InR) are preferred for research, but strict export restrictions continue to limit their use. Chinese-origin rhesus (ChR), easier to procure, are genetically distinct from InR and differ in their immune response to infectious agents, such as the Simian Immunodeficiency Virus. The most advanced malaria vac‐ cine, RTS,S (GlaxoSmithKline), is based on the circumsporozoite protein (CSP) of Plasmodium falciparum. This study was used to determine if the safety and immunogenicity outcomes following vaccination with a CSP vaccine would differ in the InR and ChR models, given the genetic differences between the two sub-populations of rhesus. RTS,S (GlaxoSmithKline Vaccines, Rixensart, Belgium) is a recombinant malaria antigen based on the circumsporozoite protein (CSP) of P. falciparum. The NPNA repeats are highly conserved across all P. falciparum strains, the C-terminal region contains polymorphic residues, which could be one of the reasons why a monovalent CSP vaccine, such as RTS,S, confers partial protection against diverse parasite strains prevalent in endemic areas [5]. In 2015, a paediatric formulation of RTS,S/AS01E (MosquirixTM) received regulatory approval, and is in pilot studies in three African countries, to determine its effectiveness in malaria control when deployed by the public health system [8]
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