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Infection and Immunity, February 2007, p. 838-845, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.01075-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Murine Immune Responses to Liver-Stage Antigen 1 Protein FMP011, a Malaria Vaccine Candidate, Delivered with Adjuvant AS01B or AS02A{triangledown}

Clara Brando,1 Lisa A. Ware,1 Helen Freyberger,1 April Kathcart,1 Arnoldo Barbosa,2 Sylvie Cayphas,3 Marie-Ange Demoitie,3 Pascal Mettens,3 D. Gray Heppner,1 and David E. Lanar1*

Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500,1 Centre de Salut Internacional, Hospital Clinic/Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, 08036 Barcelona, Spain,2 GlaxoSmithKline Biologicals, Rixensart, Belgium3

Received 10 July 2006/ Returned for modification 21 August 2006/ Accepted 1 November 2006

Liver-stage antigen 1 (LSA1) is expressed by Plasmodium falciparum only during the intrahepatic cell stage of the parasite's development. Immunoepidemiological studies in regions where malaria is endemic suggested an association between the level of LSA1-specific humoral and cell-mediated immune responses and susceptibility to clinical malaria. A recombinant LSA1 protein, FMP011, has been manufactured as a preerythrocytic vaccine to induce an immune response that would have the effect of controlling parasitemia and disease in humans. To evaluate the immunogenicity of FMP011, we analyzed the immune response of three inbred strains of mice to antigen immunization using two different adjuvant formulations, AS01B and AS02A. We report here the ability of BALB/c and A/J mice, but not C57BL/6J mice, to mount FMP011-specific humoral (antibody titer) and cellular (gamma interferon [IFN-{gamma}] production) responses following immunization with FMP011 formulated in AS01B or AS02A. Immunization of BALB/c and A/J mice with FMP011/AS01B induced more antigen-specific IFN-{gamma}-producing splenocytes than immunization with FMP011/AS02A. A slightly higher titer of antibody was induced using AS02A than AS01B in both strains. C57BL/6J mice did not respond with any detectable FMP011-specific IFN-{gamma} splenocytes or antibody when immunized with FMP011 in AS01B or AS02A. Intracellular staining of cells isolated from FMP011/AS01B-immunized BALB/c mice indicated that CD4+ cells, but not CD8+ cells, were the main IFN-{gamma}-producing splenocyte. However, inclusion of blocking anti-CD4+ antibody during the in vitro restimulation ELISpot analysis failed to completely abolish IFN-{gamma} production, indicating that while CD4+ T cells were the major source of IFN-{gamma}, other cell types also were involved.

* Corresponding author. Mailing address: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Bldg 503, Forest Glen Annex, Washington, DC 20307-5100. Phone: (301) 319-9003. Fax: (301) 319-7358. E-mail: david.lanar{at}us.army.mil.

{triangledown} Published ahead of print on 13 November 2006.

Editor: W. A. Petri, Jr.

Infection and Immunity, February 2007, p. 838-845, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.01075-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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