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Infection and Immunity, April 2008, p. 1709-1718, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01614-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of a Plasmodium falciparum Protein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1{triangledown}

Ariane Rodríguez,1 Jaap Goudsmit,1,2 Arjen Companjen,1 Ratna Mintardjo,1 Gert Gillissen,1 Dennis Tax,1 Jeroen Sijtsma,1 Gerrit Jan Weverling,1 Lennart Holterman,1 David E. Lanar,3 Menzo J. E. Havenga,1 and Katarina Radosevic1*

Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands,1 Center of Poverty-Related Communicable Diseases, Academic Medical Center, Amsterdam, The Netherlands,2 Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-75003

Received 6 December 2007/ Returned for modification 21 December 2007/ Accepted 14 January 2008

Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite (CS) protein improved significantly when the protein is primed with recombinant adenovirus serotype 35 coding for CS (rAd35.CS). The current study was designed to answer the question whether such an effect can be extended to liver-stage antigens (LSA) of Plasmodium falciparum such as LSA-1. Studies with mice have demonstrated that the LSA-1 protein induces strong antibody response but a weak T-cell immunity. We first identified T-cell epitopes in LSA-1 by use of intracellular gamma interferon (IFN-{gamma}) staining and confirmed these epitopes by means of enzyme-linked immunospot assay and pentamer staining. We show that a single immunization with rAd35.LSA-1 induced a strong antigen-specific IFN-{gamma} CD8+ T-cell response but no measurable antibody response. In contrast, vaccinations with the adjuvanted recombinant LSA-1 protein induced remarkably low cellular responses but strong antibody responses. Finally, both priming and boosting of the adjuvanted protein by rAd35 resulted in enhanced T-cell responses without impairing the level of antibody responses induced by the protein immunizations alone. Furthermore, the incorporation of rAd35 in the vaccination schedule led to a skewing of LSA-1-specific antibody responses toward a Th1-type immune response. Our results show the ability of rAd35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule without impairing the B-cell response.

* Corresponding author. Mailing address: Crucell Holland BV, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands. Phone: 31 (0)71 5199100. Fax: 31 (0)71 5199800. E-mail: Katarina.Radosevic{at}crucell.com

{triangledown} Published ahead of print on 22 January 2008.

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2008, p. 1709-1718, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01614-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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