Enhanced acquired antibodies to a chimeric Plasmodium falciparum antigen; UB05‐09 is associated with protective immunity against malaria

Abstract

SummaryIt has been shown that covalently linking two antigens could enhance the immunogenicity of the chimeric construct. To prioritize such a chimera for malaria vaccine development, it is necessary to demonstrate that naturally acquired antibodies against the chimera are associated with protection from malaria. Here, we probe the ability of a chimeric construct of UB05 and UB09 antigens (UB05‐09) to better differentiate between acquired immune protection and susceptibility to malaria. In a cross‐sectional study, recombinant UB05‐09 chimera and the constituent antigens were used to probe for specific antibodies in the plasma from children and adults resident in a malaria‐endemic zone, using the enzyme‐linked immunosorbent assay (ELISA). Anti‐UB05‐09 antibody levels doubled that of its constituent antigens, UB09 and UB05, and this correlated with protection against malaria. The presence of enhanced UB05‐09‐specific antibody correlated with the absence of fever and parasitaemia, which are the main symptoms of malaria infection. The chimera is more effective in detecting and distinguishing acquired protective immunity against malaria than any of its constituents taken alone. Online B‐cell epitope prediction tools confirmed the presence of B‐cell epitopes in the study antigens. UB05‐09 chimera is a marker of protective immunity against malaria that needs to be studied further.

Analysis of the Role of TpUB05 Antigen from Theileria parva in Immune Responses to Malaria in Humans Compared to Its Homologue in Plasmodium falciparum the UB05 Antigen

“…In previous studies from our group, the P. falciparum antigens UB05, UB09, and chimeric UB05-09 and their respective polyclonal antiserums were analyzed using ELISA, ELISpot assays, and growth inhibition assays with samples from a malaria endemic region. These findings have been published in [12][13][14]. During these same studies, we included TpUB05 and its polyclonal antiserum in separate wells on the same plates and exposed them to the same experimental conditions as the UB05 antigen.…”

“…The UB05 antigen has previously been compared to its chimeric construct, UB05-09, using an ELISpot assay, ELISA, and growth-inhibition assay, published in [12][13][14][15], respectively. During those experiments, TpUB05 was added into separate wells on the same plates and exposed to the same experimental conditions as the other study antigens/antisera.…”

Preclinical efficacy and immunogenicity assessment to show that a chimeric Plasmodium falciparum UB05‐09 antigen could be a malaria vaccine candidate

“…It has been shown that protective immunity provoked by whole organism immunization indicates the accumulation of small responses to a large number of antigens; likewise, a single antigen with one or more epitopes could be enough to illicit a protective immune response when presented to the immune system in an appropriate manner . UB05‐09 is composed of 2 antigen fragments with multiple B‐ and T‐cell epitopes as shown in previous bioinformatics analyses . It is therefore capable of stimulating both arms of the immune system to provide protection against P. yoelii infection.…”

“…33 UB05-09 is composed of 2 antigen fragments with multiple B-and T-cell epitopes as shown in previous bioinformatics analyses. 18,19 It is therefore capable of stimulating both arms of the immune system to provide protection against P. yoelii infection.…”

“…In previous studies, covalently linking UB05 and UB09 produced a UB05-09 chimera that was able to provoke interferon-gamma production in T cells 18 and detected enhanced antigen-specific antibodies in semi-immunes than malaria susceptible subjects in a significantly higher manner. 19 Hence, it was concluded that UB05-09 is a marker of protective immunity to malaria.…”