Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity.

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

[Evaluation of thermostable yellow fever vaccine from the Pasteur Institute on international travellers]. / Evaluation du vaccin antiamaril thermostable de l'Institut Pasteur chez des voyageurs internationaux.

The authors studied the tolerance and efficacy of the new stabilized 17D yellow fever vaccine produced by Pasteur Vaccins, on 50 international travellers at the University Hospital of Grenoble (France), comparing it with the standard 17D yellow fever vaccine. The short-term and long-term tolerance in all the travellers was excellent. The serological efficacy was estimated by seroneutralization assay with the vaccine virus Rockefeller 17D, which is the most sensitive and the most specific method. The seroconversion rate was 93.8%, the same as the rate obtained with the standard yellow fever vaccine in 50 other travellers. The authors studied also the serological response to the standard yellow fever vaccine associated with other vaccines (diphtheria, tetanus, oral or injectable poliomyelitis, and oral cholera): the seroconversion rates were similar to those obtained with the yellow fever vaccine alone, thus demonstrating that these associated vaccines do not interfere with immunization against yellow fever.

[IPAD-DTCP: study of the tolerability and serum antipoliomyelitic efficacy in a maternal-child health center at Pikine (Dakar)]. / IPAD DTCP: étude de tolérance et d'éfficacité serologique antipoliomyélitique dans un centre de P.M.I. de Pikine (Dakar).

A study of the tolerance and potency of a quadruple vaccine adsorbed on calcium phosphate was carried out in Senegal. After a follow up of four months the local tolerance was better when the vaccine was inoculated by intramuscular injection. A high level of passively acquired antibodies was found for the three subtypes of polioviruses and seemed to delay the immunological reaction. 90%, 96% and 92% of the total group of children involved in this study had a positive reaction.

[Controlled results of the oral anticholera vaccine from the Institut Pasteur during the Shaba-Zaire epidemic in 1983]. / Résultats contrôlés du vaccin anticholérique oral de l'Institut Pasteur au cours de l'épidémie du Shaba-Zaïre en 1983.

Pasteur Institute oral cholera vaccine has been evaluated in the district of Malemba NKulu (Zaire). A cholera epidemic began 7 months after the vaccination. 216 cholera cases occurred among 18,377 control non-vaccinated subjects and 57 cases occurred among 6,249 subjects vaccinated by the conventional parenterally administered vaccine. In contrast, only 6 cholera cases occurred among 12,014 subjects vaccinated by the oral cholera vaccine.