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Infection and Immunity, April 2006, p. 2138-2144, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2138-2144.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Reduced Protective Efficacy of a Blood-Stage Malaria Vaccine by Concurrent Nematode Infection

Zhong Su,* Mariela Segura, and Mary M. Stevenson

McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada, and McGill Centre for Host-Parasite Interactions, Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada

Received 8 September 2005/ Returned for modification 12 December 2005/ Accepted 8 January 2006

Helminth infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coinfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal nematode, Heligmosomoides polygyrus, to investigate the impact of nematode infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized nematode-infected mice produced significantly lower levels of malaria-specific antibody than nematode-free mice produced. In response to nematode and malarial antigens, spleen cells from immunized nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized nematode-free mice produced. Furthermore, H. polygyrus infection also induced a strong transforming growth factor ß1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent nematode infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.

* Corresponding author. Mailing address: Research Institute of McGill University Health Centre, Room L11-409, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada. Phone: (514) 934-1934, ext. 44508. Fax: (514) 934-8332. E-mail: zhong.su{at}mail.mcgill.ca.

Editor: J. F. Urban, Jr.

Infection and Immunity, April 2006, p. 2138-2144, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2138-2144.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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