Protection against malaria can be achieved by induction of a strong CD8 + T-cell response against the Plasmodium circumsporozoite protein (CSP), but most subunit vaccines suffer from insufficient memory responses. In the present study, we analyzed the impact of postimmunization sporozoite challenge on the development of long-lasting immunity. BALB/c mice were immunized by a heterologous prime/boost regimen against Plasmodium berghei CSP that induces a strong CD8 + T-cell response and sterile protection, which is short-lived. Here, we show that protective immunity is prolonged by a sporozoite challenge after immunization. Repeated challenges induced sporozoite-specific antibodies that showed protective capacity. The numbers of CSP-specific CD8 + T cells were not substantially enhanced by sporozoite infections; however, CSP-specific memory CD8 + T cells of challenged mice displayed a higher cytotoxic activity than memory T cells of immunized-only mice. CD4 + T cells contributed to protection as well; but CD8 + memory T cells were found to be the central mediator of sterile protection. Based on these data, we suggest that prolonged protective immunity observed after immunization and infection is composed of different antiparasitic mechanisms including CD8 + effector-memory T cells with increased cytotoxic activity as well as CD4 + memory T cells and neutralizing antibodies.
Keywords: CD8 + T cells r Plasmodium r Sporozoites r VaccinationAdditional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Susanne Tartz e-mail: tartz@bni-hamburg.de
IntroductionThere is now good progress both in the prevention and the treatment of malaria that leads to decreasing numbers of malaria cases and fatalities; nevertheless malaria is still one of the biggest C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu
694Susanne Tartz et al. Eur. J. Immunol. 2013. 43: 693-704 challenges for global public health management. There are around 250 million cases per year worldwide with the vast majority of these in the African region and it is estimated that malaria accounts for 900 000 deaths annually [1]. Therefore a vaccine is still the ultimate goal of malaria research. The development of immunity and immunological memory to Plasmodium infections in malaria endemic areas has been intensively studied [2]. Children in the age of 6 months to 5 years are at the highest risk of being infected with Plasmodium and developing severe disease. In the first years of life, an anti-disease immunity is acquired that leads to high-density infections with mild symptoms. In contrast, the acquisition of anti-parasite immunity takes years to decades, although transmigrant studies show that adults may acquire immunity more rapidly than children [3,4]. It is supposed that anti-parasite immunity is based mainly on antibodies recognising variant surface antigens on the membranes of infected erythrocytes whereas immune responses against preerythrocytic forms seem to play a m...