[HTML][HTML] Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

PV Scaria, C Anderson, O Muratova, N Alani, HV Trinh… - npj Vaccines, 2021 - nature.com
PV Scaria, C Anderson, O Muratova, N Alani, HV Trinh, ST Nadakal, I Zaidi, L Lambert…
npj Vaccines, 2021nature.com
Malaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have
advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel®
developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA
(Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies
with these conjugates revealed that non-human primates are better than mice to recapitulate
the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a …
Abstract
Malaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, 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.
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