HIC-Vac Annual Meeting 2023

Strengths and Limitations of Human Challenge Studies in Vaccine Development

De Vere Horsley Estate

1-3 November 2023

HIC-Vac (Homepage | Hic Vac (hic-vac.org)) is an international network of researchers who are developing human infection challenge (HIC) studies to accelerate the development of vaccines against pathogens of high global impact.

In early November 2023, Angela was invited to give an oral presentation on insights gained from the group’s work on human challenge models for malaria and Mimi was invited to present a poster on isolation of monoclonal antibodies against a P. vivax vaccine candidate at the HIC-Vac annual meeting in Guildford.

This year’s meeting focus was on ‘Strengths and Limitations of Human Challenge Studies in Vaccine Development’. Angela, who was joined by collaborator Wiebke Nahrendorf from the University of Edinburgh, gave a talk entitled “A human model of clinical immunity to malaria” which detailed outputs of the group’s rechallenge models for P. falciparum and P. vivax malaria. They explained how infecting healthy malaria-naïve adult volunteers up to three times over a 12-month period can track the development of “tolerance” to disease in real-time. They presented data for P. falciparum infection supporting epidemiological evidence that tolerance to severe disease is acquired early, after just the first infection of life, despite no immunity to “febrile malaria”. They further demonstrated that this is likely underpinned by the silencing of cytotoxic T cells, and how HIC-Vac pump-prime funding had enabled further delineation of these T cell responses at a single cell level. They also showed that, for P. vivax infection (in contrast to P. falciparum), immunity to “febrile malaria” (so-called “clinical” immunity) develops quickly after re-exposure to P. vivax. This occurs without any apparent effect on the parasite load in the blood. Implications for malaria-prevention strategies were discussed and there was a great deal of interest in the work from the Hic-Vac community.

Mimi presented her poster entitled ‘Characterising human monoclonal antibodies induced by vaccines against Plasmodium vivax Duffy-binding protein’ which detailed the isolation and characterisation of a panel of monoclonal antibodies (mAb) against a blood-stage vaccine candidate P. vivax Duffy-binding protein (PvDBP). Samples from volunteers who took part in the VAC071 and VAC079 trials conducted in Oxford, in which the vaccines were tested for efficacy by controlled human malaria infection, were used to isolate a large panel of mAb against PvDBP and initial characterisation has found a small number of clones with high potency in parasite growth inhibition assays. This work was supported by a Hic-Vac pump priming award.

A number of the group’s clinical trials team, including Sarah, Jo, Martino, Fran, Mimi and Angela, attended the meeting and there were many valuable discussions with experts conducting challenge studies across the globe.