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

Abstract

SummaryAlthough it is generally agreed that an effective vaccine would greatly accelerate the control of malaria, the lone registered malaria vaccine Mosquirix™ has an efficacy of 30%‐60% that wanes rapidly, indicating a need for improved second‐generation malaria vaccines. Previous studies suggested that immune responses to a chimeric Plasmodium falciparum antigen UB05‐09 are associated with immune protection against malaria. Herein, the preclinical efficacy and immunogenicity of UB05‐09 are tested. Growth inhibition assay was employed to measure the effect of anti‐UB05‐09 antibodies on P. falciparum growth in vitro. BALB/c mice were immunized with UB05‐09 and challenged with the lethal Plasmodium yoelii 17XL infection. ELISA was used to measure antigen‐specific antibody production. ELISPOT assays were employed to measure interferon‐gamma production ex vivo after stimulation with chimeric UB05‐09 and its constituent antigens. Purified immunoglobulins raised in rabbits against UB05‐09 significantly inhibited P. falciparum growth in vitro compared to that of its respective constituent antigens. A combination of antibodies to UB05‐09 and the apical membrane antigen (AMA1) completely inhibited P. falciparum growth in culture. Immunization of BALB/c mice with recombinant UB05‐09 blocked parasitaemia and protected them against lethal P. yoelii 17XL challenge infection. These data suggest that UB05‐09 is a malaria vaccine candidate that could be developed further and used in conjunction with AMA1 to create a potent malaria vaccine.

Surface Engineering of the RNA Coliphage Q? to Display Plasmodium Falciparum Derived Asexual Blood Stage Antigens UB05 and Merozoite Surface Protein 3

“…This is mainly because this region is not only conserved across different parasite strains [21][22][23]; but equally possessed epitopes confirmed to be targeted by antibodies associated with protection [18,23]. Similarly UB05 antigen specific immune responses have been reported as a potential marker of protective immunity against malaria [14,24,25].…”

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

“…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.…”

“…As previously mentioned [15], all laboratory strains were generously donated by the MR4/BEI Resources, NIAID, NIH, Manassas, VA. The following P. falciparum laboratory strains were used:…”

“…As previously mentioned [15], all laboratory strains were generously donated by the MR4/BEI Resources, NIAID, NIH, Manassas, VA. The following P. falciparum laboratory strains were used: FCR-1/FVO (MRA-909, contributed by W. Trager), 3D7 (MRA-102, contributed by Daniel J. Carucci), and HB3 (MRA-155, contributed by Thomas E. Wellems) for the in vitro assay.…”

Analysis of the role of TpUB05 antigen from Theileria parva in immune responses to malaria in humans compared to its homologue in Plasmodium falciparum; UB05 antigen

“…In previous studies in our group, the P. falciparum antigens; UB05, UB09 and chimeric UB05-09 and their respective polyclonal antiserum were analysed using ELISA, ELISpot assay and Growth Inhibition Assay with samples from a malaria endemic region (Dinga et al, 2016(Dinga et al, , 2017(Dinga et al, , 2018. 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 UB05 antigen.…”