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Clinical and Vaccine Immunology, November 2008, p. 1674-1683, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00164-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immune Responses of Mice with Different Genetic Backgrounds to Improved Multiepitope, Multitarget Malaria Vaccine Candidate Antigen FALVAC-1A {triangledown}

S. A. Kaba,1,{dagger} A. Price,1,2 Z. Zhou,1,2 V. Sundaram,1 P. Schnake,1 I. F. Goldman,1 A. A. Lal,1 V. Udhayakumar,1 and C. W. Todd1,2*

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341,1 Atlanta Research and Education Foundation, Decatur, Georgia 300332

Received 7 May 2008/ Returned for modification 11 June 2008/ Accepted 29 August 2008

FALVAC-1A is a second-generation multitarget, multiepitope synthetic candidate vaccine against Plasmodium falciparum, incorporating elements designed to yield a stable and immunogenic molecule. Characteristics of the immunogenicity of FALVAC-1A were evaluated in congenic (H-2b, H-2k, and H-2d) and outbred strains of mice. The influences of four adjuvants (aluminum phosphate, QS-21, Montanide ISA-720, and copolymer CRL-1005) on different aspects of the immune response were also assessed. FALVAC-1A generated strong antibody responses in all mouse strains. The highest mean enzyme-linked immunosorbent assay (ELISA) antibody concentrations against FALVAC-1A were observed in the outbred ICR mice, followed by B10.BR, B10.D2, and C57BL/6 mice, though this order varied for the different adjuvants, with no statistical differences between mouse strains. In all mouse strains, the highest anti-FALVAC-1A antibody titers in ELISAs were induced by FALVAC-1A in copolymer and ISA-720 formulations, followed by QS-21 and AlPO4. These antibodies were of all four subclasses, though immunoglobulin G1 (IgG1) predominated, with the exception of FALVAC-1A with the QS-21 adjuvant, which induced predominantly IgG2c responses. Both sporozoites and blood stages of P. falciparum were recognized by anti-FALVAC-1A sera in the immunofluorescence assay. In addition to antibody, cellular immune responses were detected; these responses were studied by examining spleen cells producing gamma interferon and interleukin-4 in enzyme-linked immunospot assays. In summary, FALVAC-1A was found to be highly immunogenic and elicited functionally relevant antibodies that can recognize sporozoites and blood-stage parasites in diverse genetic backgrounds.

* Corresponding author. Mailing address: Division of Parasitic Diseases, 4770 Buford Highway, MS F-36, Centers for Disease Control and Prevention, Atlanta, GA 30341. Phone: (770) 488-4526. Fax: (770) 488-4253. E-mail: ckt1{at}cdc.gov

{triangledown} Published ahead of print on 10 September 2008.

{dagger} Present address: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910.

Clinical and Vaccine Immunology, November 2008, p. 1674-1683, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00164-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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