Optimizing malaria transmission-blocking vaccines with improved platforms

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

In FY2022, LMIV scientists published a research article that applied our protein-protein conjugation platform to develop novel COVID-19 vaccines, and a research article in which we explored a novel liposome-based vaccine platform with colleagues at SUNY-Buffalo. 1. Scaria PV, Anderson C, Muratova O, Alani N, Trinh HV, Nadakal ST, Zaidi I, Lambert LE, Beck Z, Barnafo EK, Rausch KM, Rowe C, Chen B, Matyas GR, Rao M, Alving CR, Narum DL, Duffy PE. Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques. 2021. npjVaccines. Dec 9. In this study, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity. 2. Scaria PV, Rowe CG, Chen BB, Dickey TH, Renn JP, Lambert LE, Barnafo EK, Rausch KM, Tolia NH, Duffy PE. Protein-protein conjugation enhances immunogenicity of SARS-CoV-2 Receptor Binding Domain (RBD) vaccines. 2022. iScience. Jul 9. In this study, we adapted our protein-protein conjugate vaccine technology to generate a vaccine based on receptor-binding domain (RBD) antigen. RBD was conjugated to a carrier protein, EcoCRM, to generate two types of conjugates: crosslinked and radial conjugates. In the crosslinked conjugate, antigen and carrier are chemically crosslinked; in the radial conjugate, the antigen is conjugated to the carrier by site-specific conjugation. With AS01 adjuvant, both conjugates showed enhanced immunogenicity in mice compared to RBD, with a Th1 bias. In hACE2 binding inhibition and pseudovirus neutralization assays, sera from mice vaccinated with the radial conjugate demonstrated strong functional activity. We have initiated further evaluation of this conjugate in non-human primates. In addition, we have initiated efforts to generate conjugates of RBD corresponding to Omicron variants of SARA-CoV-2 to develop vaccine candidates targeted to Omicron variants.