Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform

Abstract

Malaria remains one of the world’s most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an effective vaccine; but the leading P. falciparum and P. vivax vaccine candidates, RTS,S and VMP001, show only modest to low field efficacy. New antigens and improved ways for screening antigens for protective efficacy will be required. This study exploits the potential of Virus-Like Particles (VLP) to enhance immune responses to antigens, the ease of coupling peptides to the Q beta (Qβ) VLP and the existing murine malaria challenge to screen B-cell epitopes for protective efficacy. We screened P. vivax TRAP (PvTRAP) immune sera against individual 20-mer PvTRAP peptides. The most immunogenic peptides associated with protection were loaded onto Qβ VLPs to assess protective efficacy in a malaria sporozoite challenge. A second approach focused on identifying conserved regions within known sporozoite invasion proteins and assessing them as part of the Qβ. Using this VLP as a peptide scaffold, four new protective B-cell epitopes were discovered: three from the disordered region of PvTRAP and one from Thrombospondin-related sporozoite protein (TRSP). Antigenic interference between these and other B-cell epitopes was also explored using the virus-like particle/peptide platform. This approach demonstrates the utility of VLPs to help identifying new B-cell epitopes for inclusion in next-generation malaria vaccines.

Immunogenicity of Multi-Target Chimeric RHDV Virus-Like Particles Delivering Foreign B-Cell Epitopes

“…In summary, the results obtained indicated that the bivalent chimeric RHDV VLPs allowed good simultaneous immunogenicity for both target B-cell epitopes tested, in agreement with previous reports with other chimeric VLPs [42,[45][46][47]. Interestingly, RHDV VLPs have been recently reported to efficiently co-deliver two T-cell epitopes (cancer antigens), inducing a targeted anti-tumour immune response [14,15], further extending the feasibility of using the RHDV vaccine platform for the co-delivery of multiple antigens.…”

“…Several VLP-based platforms have been proposed as scaffolds for multi-target antigen presentation [40][41][42][43][44][45][46][47]. Potential concerns faced by multivalent vaccines are issues related to immune interference and epitope dominance, as numerous reports have shown that co-immunization with multiple antigens can induce immune interference, affecting both antigen specific B cell responses and T cell responses [48][49][50][51][52].…”

“…Potential concerns faced by multivalent vaccines are issues related to immune interference and epitope dominance, as numerous reports have shown that co-immunization with multiple antigens can induce immune interference, affecting both antigen specific B cell responses and T cell responses [48][49][50][51][52]. Indeed, in certain cases, multivalent VLPs have failed to induce a strong immune response against an incorporated epitope, in contrast to cognate monovalent VLPs, reflecting problems associated with epitope dominance or inadequate antigen presentation [41,43,45,47]. With this in mind, our aim in this study was to explore the feasibility of developing RHDV-based engineered VLPs as efficient multivalent vaccines co-delivering different foreign B-cell antigens.…”

Identification, Selection and Immune Assessment of Liver Stage CD8 T Cell Epitopes From Plasmodium falciparum

“…Antibody responses to each of these three proteins have been detected in individuals naturally infected with either P. falciparum or P. vivax (54)(55)(56). However, unlike PF08_0081 and PF14_0593, B cell epitopes specific for PFD0430c have yet to be identified (57), despite that fact that of the three proteins PFD0430c is the best characterized. PFD0430c was first identified by transcriptome analysis of P. yoelii salivary gland sporozoites, and was located in the microneme (58).…”

VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants

“…VLPs can be expressed in insect [32,47], mammalian [48,49], bacterial [50], plant [37,51] or yeast cells [33]. These particles have been used for the development of vaccines against several infectious diseases [52].…”