Antibody response of a particle-inducing, liposome vaccine adjuvant admixed with a Pfs230 fragment

Wei-Chiao Huang; Bingbing Deng; Amal Seffouh; Joaquin Ortega; Carole A Long; Ragavan V Suresh; Xuedan He; Kazutoyo Miura; Shwu-Maan Lee; Yimin Wu; Jonathan F Lovell

doi:10.1038/s41541-020-0173-x

Antibody response of a particle-inducing, liposome vaccine adjuvant admixed with a Pfs230 fragment

NPJ Vaccines. 2020 Mar 18;5(1):23. doi: 10.1038/s41541-020-0173-x. eCollection 2020.

Authors

Affiliations

¹ 1Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260 USA.
² 2Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 USA.
³ 3Department of Anatomy and Cell Biology, McGill University Montreal, QC, H3A 0C7 Canada.
⁴ PATH's Malaria Vaccine Initiative (MVI), Washington, DC 20001 USA.

Abstract

Pfs230 is a malaria transmission-blocking antigen candidate, expressed on the surface of Plasmodium falciparum gametocytes. A recombinant, his-tagged Pfs230 fragment (Pfs230C1; amino acids 443-731) formed serum-stable particles upon incubation with liposomes containing cobalt-porphyrin-phospholipid (CoPoP). In mice, immunization with Pfs230C1, admixed with the adjuvants Alum, Montanide ISA720 or CoPoP liposomes (also containing synthetic monophosphoryl lipid A; PHAD), resulted in elicitation of IgG antibodies, but only those induced with CoPoP/PHAD or ISA720 strongly reduced parasite transmission. Immunization with micrograms of Pfs230C1 adjuvanted with identical liposomes lacking cobalt (that did not induce particle formation) or Alum was less effective than immunization with nanograms of Pfs230C1 with CoPoP/PHAD. CoPoP/PHAD and ISA720 adjuvants induced antibodies with similar Pfs230C1 avidity but higher IgG2-to-IgG1 ratios than Alum, which likely contributed to enhanced functional activity. Unlike prior work with another transmission-blocking antigen (Pfs25), Pfs230C1 was found to be effectively taken up by antigen-presenting cells without particle formation. The anti-Pfs230C1 IgG response was durable in mice for 250 days following immunization with CoPoP/PHAD, as were antibody avidity and elevated IgG2-to-IgG1 ratios. Immunization of rabbits with 20 µg Pfs230C1 admixed with CoPoP/PHAD elicited antibodies that inhibited parasite transmission. Taken together, these results show that liposomes containing CoPoP and PHAD are an effective vaccine adjuvant platform for recombinant malaria transmission blocking antigens.

Keywords: Biotechnology; Immunology.

Abstract

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