Liposomes containing monophosphoryl lipid A and QS-21 serve as an effective adjuvant for soluble circumsporozoite protein malaria vaccine FMP013.

Abstract

Malaria caused by Plasmodium falciparum continues to threaten millions of people living in the tropical parts of the world. A vaccine that confers sterile and life-long protection remains elusive despite more than 30years of effort and resources invested in solving this problem. Antibodies to a malaria vaccine candidate circumsporozoite protein (CSP) can block invasion and can protect humans against malaria. We have manufactured the Falciparum Malaria Protein-013 (FMP013) vaccine based on the nearly full-length P. falciparum CSP 3D7 strain sequence. We report here immunogenicity and challenge data on FMP013 antigen in C57BL/6 mice formulated with two novel adjuvants of the Army Liposome Formulation (ALF) series and a commercially available adjuvant Montanide ISA 720 (Montanide) as a control. ALF is a liposomal adjuvant containing a synthetic monophosphoryl lipid A (3D-PHAD®). In our study, FMP013 was adjuvanted with ALF alone, ALF containing aluminum hydroxide (ALFA) or ALF containing QS-21 (ALFQ). Adjuvants ALF and ALFA induced similar antibody titers and protection against transgenic parasite challenge that were comparable to Montanide. ALFQ was superior to the other three adjuvants as it induced higher antibody titers with improved boosting after the third immunization, higher serum IgG2c titers, and enhanced protection. FMP013+ALFQ also augmented the numbers of splenic germinal center-derived activated B-cells and antibody secreting cells compared to Montanide. Further, FMP013+ALFQ induced antigen-specific IFN-γ ELISPOT activity, CD4+ T-cells and a TH1-biased cytokine profile. These results demonstrate that soluble CSP can induce a potent and sterile protective immune response when formulated with the QS-21 containing adjuvant ALFQ. Comparative mouse immunogenicity data presented here were used as the progression criteria for an ongoing non-human primate study and a regulatory toxicology study in preparation for a controlled human malaria infection (CHMI) trial.

• Authors: Christopher J Genito, Zoltan Beck, Timothy W Phares, Fanta Kalle, Keith J Limbach, Maureen E Stefaniak, Noelle B Patterson, Elke S Bergmann-Leitner, Norman C Waters, Gary R Matyas, Carl R Alving, Sheetij Dutta
• Journal: Vaccine (Vaccine) Vol. 35 Issue 31 Pg. 3865-3874 (07 05 2017) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 28596090 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Adjuvants, Immunologic
• Antibodies, Protozoan
• Lipid A
• Liposomes
• Malaria Vaccines
• Protozoan Proteins
• Saponins
• circumsporozoite protein, Protozoan
• saponin QA-21V1
• Interferon-gamma
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antibodies, Protozoan (blood)
• B-Lymphocytes (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Disease Models, Animal
• Enzyme-Linked Immunospot Assay
• Female
• Interferon-gamma (metabolism)
• Lipid A (administration & dosage, analogs & derivatives)
• Liposomes (administration & dosage)
• Malaria Vaccines (administration & dosage, immunology)
• Malaria, Falciparum (prevention & control)
• Mice, Inbred C57BL
• Protozoan Proteins (immunology)
• Saponins (administration & dosage)