Human antibodies from vaccinated volunteers are being turned into a blueprint for next-generation vaccines and injectable antibody therapies against malaria. This matters because even when people are vaccinated against diseases like malaria, their immune systems often fail to produce enough effective antibodies. The researchers aim to solve this by first isolating the best human antibodies from volunteers who received leading malaria vaccines, then using those antibodies to design improved vaccine components and to create potent antibody mixtures that can be delivered directly—bypassing the need for the body to generate its own immune response. If successful, this approach could transform how we protect against the most stubborn infectious diseases. Rather than relying solely on traditional vaccines that may not work well, doctors could give patients a pre-made cocktail of powerful human antibodies, either as an injection or through a viral vector that instructs cells to produce them. This would be especially valuable for malaria, which kills hundreds of thousands of people each year, but the same platform could be adapted for other difficult disease targets where conventional vaccination has fallen short.
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Antibodies underpin effective vaccine-induced immunity, whilst monoclonal antibodies (mAbs) have come of age as effective biologicals. Nevertheless, effective antibody-mediated immunity can still fail to arise against numerous disease targets. This proposal seeks to understand the human antibody response against target antigens to enable the development of new vaccines or immunoprophylactic approaches that can deliver effective immunity against the most challenging of human diseases. The approac hes explored here will be applicable to a range of difficult disease areas, but proof-of-concept will be established against the blood-stage human malaria parasites. This work will address four key questions: 1. Can highly effective next-generation vaccines be developed by elucidating the most quantitatively susceptible epitopes identified from the repertoire of human antibodies following vaccination? 2. Can a highly effective and synergistic combination of human mAbs be developed against th e malaria parasite? 3. Can the affinity of vaccine-induced antibodies be influenced by the means of vaccine delivery in humans? 4. Can effective immunity based on a mixture of mAbs or their defined epitopes be i) delivered using vectored technologies, or ii) induced by traditional vaccination? Human mAbs will be produced from B cells isolated from volunteers vaccinated with leading antigens from the human malaria parasites Plasmodium falciparum and P. vivax. The mAbs will be characterised and used in structural studies to aid design of improved vaccine immunogens and to assess affinity maturation. In parallel technologies will be developed that seek to bypass the adaptive immune system and deliver effective immunoprophylaxis through vectored mAb delivery.
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