Conference Agenda

Human hookworm infection, primarily caused by Necator americanus, remains a major global health burden, with vaccine development limited by insufficient identification of protective antigens. This study utilised a proteome microarray of recombinant secreted proteins from adult N. americanus, screened with sera from individuals vaccinated with irradiated third-stage larvae (iL3), to identify immunodominant targets. Selected antigens were characterised and their orthologs identified in the rodent hookworm Nippostrongylus brasiliensis.

Recombinant orthologs were evaluated in a mouse challenge model. One antigen, NBR17057 (ortholog of Na_11335), conferred significant protection, reducing intestinal worm burden and faecal egg output (p < 0.05) and inducing strong antigen-specific IgG responses. These findings support Na_11335 as a promising subunit vaccine candidate targeting the infective larval stage. Additional L3-stage antigens are being investigated to discover an effective novel human vaccine.

Multi-stage, multi-antigen vaccination against malaria is a favoured strategy to improve on the modest efficacy offered by existing vaccines. However, current multi-stage vaccine design neglects the extensive antigenic diversity which exists within populations of Plasmodium falciparum circulating in endemic areas, which has contributed to the low efficacy of multiple single-stage candidates. Using parasite genomes from the MalariaGEN Pf8 release, we combined population genetics with immunoinformatics to assess the potential for vaccine escape of the pre-erythrocytic and blood-stage targets CSP and RH5. We found that the proportion of parasites in sub-Saharan Africa encoding both vaccine-matched alleles for these targets was very low. When we predicted the effects of observed amino acid substitutions on antibody and HLA binding, we found no impact on the RH5 component of the vaccine. However, the majority of parasites sampled had the potential to escape both anti-CSP C-terminal antibodies and vaccine-induced CD4+ T-cell memory responses. We conclude that CSP-based vaccines as components of multi-stage vaccines may not provide the advantage of increased efficacy due to pre-existing polymorphisms in the C-terminal of CSP.

Introduction: Malaria remains a significant health problem. Globally, 282 million malaria cases and 610,000 malaria deaths occurred in 2024. The WHO recommends RTS,S/AS01 and R21-Matrix-M pre-erythrocytic vaccines to prevent malaria in children <5 yrs in moderate-to-high transmission settings. These vaccines are only partially effective. Evidence suggests that pre-erythrocytic vaccines are not boosted by natural malaria infection. We therefore assessed whether a whole-parasite blood-stage vaccine is more efficient in the presence of a malaria infection.

Methods: Different groups of mice received a controlled malaria infection with P. yoelii before or after vaccination. Mice were vaccinated with three doses of either killed 10⁵, 10⁶ or 10⁷ P. yoelii pRBCs formulated with the liposomal adjuvant, CAF01. Four weeks after the final vaccine dose or controlled malaria infection, mice from each group were challenged with homologous parasites.

Results: A priming malaria infection did not provide additional protection against parasitaemia to mice that received 10⁷ or 10⁶ P. yoelii pRBCs in the vaccine; however, it provided additional protection to those vaccinated with a lower dose. Boosting vaccination with malaria infection enhanced control of parasitaemia in all vaccinated groups. Reducing parasite vaccine doses in the presence of infection would lower the cost of vaccinating populations.