4.5 Article

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

Journal

VACCINE
Volume 35, Issue 31, Pages 3865-3874

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2017.05.070

Keywords

Adjuvant; Malaria; Vaccine; Liposomes; ALFQ; Monophosphoryl lipid A; QS-21; Plasmodium falciparum; Circumsporozoite protein; FMP013

Funding

  1. USAID Malaria Vaccine Development Program
  2. Henry M. Jackson Foundation [W81XWH-07-2-067]
  3. U.S. Army Medical Research and Materiel Command (MRMC) [W81XWH-07-2-067]
  4. Walter Reed Army Institute of Research
  5. United States Agency for International Development Malaria Vaccine Program

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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 30 years 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 (R)). 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-gamma ELISPOT activity, CD41(+) T-cells and a T(H)1-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. Published by Elsevier Ltd.

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