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

Puthupparampil V Scaria; Charles Anderson; Olga Muratova; Nada Alani; Hung V Trinh; Steven T Nadakal; Irfan Zaidi; Lynn Lambert; Zoltan Beck; Emma K Barnafo; Kelly M Rausch; Chris Rowe; Beth Chen; Gary R Matyas; Mangala Rao; Carl R Alving; David L Narum; Patrick E Duffy

doi:10.1038/s41541-021-00407-3

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

NPJ Vaccines. 2021 Dec 9;6(1):148. doi: 10.1038/s41541-021-00407-3.

Authors

Puthupparampil V Scaria¹, Charles Anderson¹, Olga Muratova¹, Nada Alani¹, Hung V Trinh^{2

3}, Steven T Nadakal¹, Irfan Zaidi¹, Lynn Lambert¹, Zoltan Beck^{2

3

4}, Emma K Barnafo¹, Kelly M Rausch¹, Chris Rowe¹, Beth Chen¹, Gary R Matyas², Mangala Rao², Carl R Alving², David L Narum¹, Patrick E Duffy⁵

Affiliations

¹ Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD, 20892-2903, USA.
² U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
³ Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
⁴ Pfizer, Vaccine Research and Development, Pearl River, NY, USA.
⁵ Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, 29 Lincoln Drive, Building 29B, Bethesda, MD, 20892-2903, USA. patrick.duffy@nih.gov.

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.