Pre-clinical development and assessment of viral vectors expressing a fusion antigen of P. falciparum LSA1 and LSAP2 for efficacy against liver-stage malaria
Halbroth BR., Sebastian S., Salman AM., Ulaszewska M., Gola A., Longley RJ., Janse CJ., Khan SM., Hill AVS., Spencer AJ.
<jats:p>Despite promising progress in malaria vaccine development in recent years, an efficacious subunit vaccine against <jats:italic>P. falciparum</jats:italic> (Pf) remains to be licensed and deployed. Cell mediated protection from liver-stage malaria is reliant on a sufficient number of antigen specific T cells reaching the liver during the time that parasites are present. A single vaccine expressing two antigens could potentially increase both the size and breadth of antigen specific response, while halving vaccine production cost. In this study we investigated combining two liver stage antigens PfLSA1 and PfLSAP2, and investigated induction of protective efficacy by co-administration of single-antigen vectors or vaccination with dual-antigen vectors, using simian Adenovirus and Modified Vaccinia Ankara Virus vectors. Efficacy of these vaccines was assessed in mouse malaria challenge models using chimeric <jats:italic>P. berghei</jats:italic> parasites expressing the relevant Pf antigens and challenging mice at the peak of T cell response. Vaccination with a combination of the single-antigen vectors expressing PfLSA1 or PfLSAP2 was shown to improve protective efficacy compared to vaccination with each single antigen vector alone. Vaccination with dual-antigen vectors expressing both PfLSA1 and PfLSAP2 resulted in responses to both antigens, particularly in outbred mice, and most importantly efficacy was equivalent to vaccination with a mixture of single-antigen vectors. Based on this promising data, dual-antigen vectors expressing PfLSA1 and PfLSAP2 will now proceed to GMP manufacturing and clinical assessment.</jats:p>