Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice

Intestinal parasitic nematode diseases infect over one billion people and cause significant disease burden in children (growth and cognitive stunting, malnutrition), in pregnant women, and via their dampening of the immune system in infected individuals. In over thirty years, no new classes of anti-roundworm drugs (anthelmintics) for treating humans have been developed. Because of limitations of the current drugs and the threat of parasite resistance, new anthelmintics are needed. The soil bacterium Bacillus thuringiensis (Bt) produces crystal (Cry) proteins that specifically target and kill insects and nematodes and is used around the world as a safe insecticide. Here we test the effects of the Bt Cry protein Cry5B on a chronic, natural intestinal roundworm infection in mice, namely the helminth parasite Heligmosomoides bakeri. We find that a single dose of Cry5B can eliminate 70% of the parasites and can almost completely block the ability of the parasites to produce progeny. Comparisons of Cry5B's efficacy with known anthelmintics suggest its activity is as good as or perhaps even better than those currently used. Furthermore, this protein is rapidly digested by simulated stomach juices, suggesting that protecting it from these juices would reveal a superior anthelmintic

Design and methods of a longitudinal study investigating the impact of antiretroviral treatment on the partnerships and sexual behaviour of HIV-infected individuals in rural KwaZulu-Natal, South Africa

BACKGROUND: Diagnosed HIV-infected people form an increasingly large sub-population in South Africa, one that will continue to grow with widely promoted HIV testing and greater availability of antiretroviral therapy (ART). For HIV prevention and support, understanding the impact of long-term ART on family and sexual relationships is a health research priority. This includes improving the availability of longitudinal demographic and health data on HIV-infected individuals who have accessed ART services but who are not yet ART-eligible.DESIGN AND METHODS: The aim of the study is to investigate the impact of ART on family and partner relationships, and sexual behaviour of HIV-infected individuals accessing a public HIV treatment and care programme in rural South Africa. HIV-infected men and women aged 18 years or older attending three clinics are screened. Those people initiating ART because they meet the criteria of WHO stage 4 or CD4 ? 200 cells/?L are assigned to an 'ART initiator' group. A 'Monitoring' group is composed of people whose most recent CD4 count was >500 cells/?L and are therefore, not yet eligible for ART. During the four-year study, data on both groups is collected every 6 months during clinic visits, or where necessary by home visits or phone. Detailed information is collected on social, demographic and health characteristics including living arrangements, past and current partnerships, sexual behaviour, HIV testing and disclosure, stigma, self-efficacy, quality of family and partner relationships, fertility and fertility intentions, ART knowledge and attitudes, and gender norms. Recruitment for both groups started in January 2009. As of October 2010, 600 participants have been enrolled; 386 in the ART initiator group (141, 37% male) and 214 in the Monitoring group (31, 14% male). Recruitment remains open for the Monitoring group.DISCUSSION: The data collected in this study will provide valuable information for measuring the impact of ART on sexual behaviour, and for the planning and delivery of appropriate interventions to promote family and partner support, and safe sexual behaviour for people living with HIV in this setting and elsewhere in sub-Saharan Africa

IP-10-Mediated T Cell Homing Promotes Cerebral Inflammation over Splenic Immunity to Malaria Infection

Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis

Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3(int) B220(+) γδ T cells with double-negative CD4 (−) CD8(−) phenotype in the liver

DBA/2 (H-2(d)) mice are known to be more resistant than C57BL/6 (B6, H-2(b)) mice to the non-lethal 17XNL strain of Plasmodium yoelii. This is a very strange phenomenon because the functions of conventional T cells, especially CD8(+) T cells, are known to be somewhat lower in DBA/2 mice than in other strains of mice. We examined herein how immune responses differed between DBA/2 mice and B6 mice during malarial infection. DBA/2 mice and (DBA/2 × B6)F(1) (BDF(1), H-2(b/d)) mice were found to have milder parasitaemia and to recover more quickly from malarial infection than B6 mice. These DBA/2 and BDF(1) mice were also found to experience a marked expansion of interleukin (IL)-2Rβ(+) CD3(int) cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220(+) T cells) was also marked in DBA/2 and BDF(1) mice. The majority of B220(+) T cells were γδ T cells and these T cells were double-negative CD4(−) CD8(−). More importantly, the production of immunoglobulin M (IgM)-type anti-DNA autoantibody was also higher in DBA/2 and BDF(1) mice than in B6 mice. In conjunction with data on cytokine production, these results indicate that primitive T and B cells, namely autoreactive extrathymic T cells and autoantibody-producing B cells, may be much more activated in DBA/2 mice and therefore resistant to the non-lethal 17XNL strain of P. yoelii