1 1 regression. Relative risk (proportion affected) was used to evaluate VE against severe malaria. The primary analysis was conducted on the RTS,S/AS01 MALARIA VACCINE CANDIDATE PHASE III according to protocol population; an analysis on the intention to treat SAFETY EVALUATION IN AFRICAN INFANTS 6-12 WEEKS OF population was also performed. Anti-CS antibody titers were measured AGE AT FIRST VACCINATION OVER FOURTEEN MONTHS OF with a validated ELISA test at enrolment and 1 month post dose 3. VE FOLLOW-UP against first or only episode of clinical malaria, against multiple episodes of clinical malaria and VE against severe malaria will be presented. Anti-CS Patricia Njuguna antibody response at 1 month post dose 3 will be presented. These results Kenya Medical Research Institute - Wellcome Trust, Kilifi, Kenya will contribute to the ongoing discussion on the potential role of this The RTS,S/AS01 candidate malaria vaccine is being evaluated in an vaccine in malaria control programs in sub Saharan Africa. ongoing Phase III double-blind randomized trial at 11 research centers in 7 African countries (NCT00866619). The trial has enrolled 15,460 3 children in two age categories, 5-17 months (N=8923) and 6-12 weeks old at first vaccination (N=6537). In October 2011, the results for the HETEROLOGOUS PRIME-BOOST VACCINATION WITH first co-primary endpoint were published including safety data for each CANDIDATE MALARIA VACCINES CHAD63 ME-TRAP AND age category up to 31st May 2011, as reported previously. Here we report MVA.ME-TRAP IS SAFE AND HIGHLY IMMUNOGENIC FOR the results of safety evaluation when all infants 6-12 weeks of age at EFFECTOR T-CELL INDUCTION IN HEALTHY GAMBIAN first vaccination have been followed-up for 14 months after the first INFANTS vaccine dose. Infants aged 6-12 weeks whose parents provided informed Muhammed O. Afolabi1, Jane U. Adetifa1, Abdoulie Drammeh1, consent were randomized 2:1 to receive the RTS,S/AS01 candidate malaria Nicholas Anagnostou2, Carly Bliss2, Susanne Sheehy2, Alison vaccine or a comparator vaccine (meningococcal C conjugate vaccine), Lawrie2, Rachel Roberts2, Katie Ewer2, Ya Jankey Jagne1, Nicola administered monthly for 3 doses, in coadministration with a DTPwHepB/ Viebig3, Babatunde Imoukhuede3, Adrian V. Hill2, Kalifa A. Bojang1 Hib vaccine and an oral polio vaccine. Access to clinical evaluation and 1 2 care were facilitated in all study centers. Safety analyses were performed Medical Research Council, Banjul, Gambia, The Jenner Institute, 3 on the intention-to-treat population. The following safety results will be Oxford University, Oxford, United Kingdom, European Vaccine Initiative, presented: solicited local and general reactogenicity occurring within 7 Heidelberg, Germany days post vaccination and unsolicited adverse events (AEs) within 30 days As the global community looks forward to the 2015 target for achieving post vaccination in a subset of 200 subjects from each center (N=2200). Millennium Development Goal of combating the scourge of malaria, Rashes and mucocutaneous changes collected within 30 days post efforts to develop an effective malaria vaccine are being scaled up. vaccination in the same subset (N=2200) will be presented according to Such a vaccine would complement existing control strategies against the Brighton Collaboration Guidelines. Serious adverse events (SAEs) (all, the devastating effect of malaria, which is responsible for the death fatal, related) will be reported for all infants 6-12 weeks old (N=6537) over of approximately 750,000 people per year, mostly infants and under- a 14-month period after the first vaccine dose. Unsolicited AEs and SAEs five children. We have previously reported an excellent safety and will be reported classified by MedDRA preferred term. The evaluation of immunogenicity profile of the candidate malaria vaccines, ChAd63 ME- the safety profile of RTS,S/AS01 in coadministration with the standard TRAP and MVA ME-TRAP, in Gambian adults and children. This is a follow- EPI vaccines will be key in determining whether the candidate vaccine is up report of interim findings of evaluation of these vaccines in Gambian suitable for implementation in future vaccination programs in sub-Saharan infants aged 5-12 months and 10 weeks. Twenty-four healthy infants Africa. aged 5-12 months were randomized to receive low or high dose ChAd63 prime vaccination followed by MVA boost vaccination eight weeks later 2 and 12 unvaccinated controls were enrolled in parallel. This was followed sequentially by randomization of another 36 infants aged 10 weeks in RTS,S/AS01 MALARIA VACCINE CANDIDATE PHASE III the same manner. Safety of the vaccines was assessed by the description EVALUATION: VACCINE EFFICACY AGAINST CLINICAL AND of adverse events related to vaccination, as ascertained through clinical SEVERE MALARIA IN AFRICAN INFANTS 6-12 WEEKS OF AGE assessment and biochemical and haematological tests. Immunogenicity AT FIRST VACCINATION OVER ONE YEAR OF FOLLOW-UP was evaluated by interferon-gamma ELISPOT, and intra-cellular cytokine staining and flow cytometry. The mean haemoglobin, WBC, ALT and John P. Lusingu creatinine at pre and post-vaccination visits in the low-high dose ChAd63/ RTSS Clinical Trial Partnership, National Institute for Medical Research, MVA and control groups were within acceptable ranges. Observed adverse Tanga, United Republic of Tanzania events that appeared related to vaccination included fever and induration The protective efficacy of RTS,S/AS01 candidate malaria vaccine is being at injection site but overall, the vaccination regime was very well tolerated. evaluated in an ongoing multi-center Phase III double-blind randomized Strong antigen-specific T-cell responses were observed post-MVA trial conducted in 7 African countries (NCT00866619). In October 2011, vaccination in the 5-12 month and 10 week old infants and similar levels the result of the first co-primary endpoint in children aged 5-17 months persisted after day 105. Despite the concern that induced T cell immune at first vaccination over 12 months of follow-up was published. We now responses would be weak in very young infants because they are fairly Th2 present the result of the second co-primary endpoint assessing vaccine switched, our findings suggest that heterogonous prime-boost vaccination efficacy (VE) against clinical malaria during 12 months post-vaccination with ChAd63 ME-TRAP followed by MVA ME-TRAP continues to exhibit in infants enrolled at 6-12 weeks of age. The trial has enrolled 15,460 satisfactory safety and potent T-cell immunogenicity in infants living in a children in two age categories, 5-17 months (n=8923) and 6-12 weeks malaria-endemic area. These findings support assessment of efficacy of old at first vaccination (n=6537). Infants aged 6-12 weeks whose parents this vaccination approach in infants and young children. provided informed consent were randomized 2:1 to receive the RTS,S/ AS01 candidate malaria vaccine or a comparator vaccine (meningococcal C conjugate vaccine), administered monthly for 3 doses, in coadministration with routine childhood vaccines. Clinical malaria episodes were captured by passive case detection. A standardized clinical algorithm for evaluation of sick children was used to identify severe malaria cases in children presenting to clinical facilities. VE against first clinical episodes was evaluated using hazard rate by Cox regression modelling. VE against all episodes was evaluated using incidence rates by negative binomial www.astmh.org 2 4 5 PHASE 1 WITH SPOROZOITE CHALLENGE TRIAL: AN OPEN- CONSENSUS ON STANDARDIZATION OF CONTROLLED LABEL DOSE-ESCALATION SAFETY, REACTOGENICITY, HUMAN MALARIA INFECTION BY MOSQUITO BITE FOR IMMUNOGENICITY, AND EFFICACY STUDY OF THE VACCINE EVALUATION OF CANDIDATE MALARIA VACCINES CANDIDATE PLASMODIUM FALCIPARUM MALARIA PROTEIN Matthew B. Laurens1, Christopher J. Duncan2, Judith E. Epstein3, (FMP012), AN E. COLI-EXPRESSED CELL-TRAVERSAL Adrian V. Hill2, Jack L. Komisar4, Kirsten E. Lyke5, Christian F. PROTEIN FOR OOKINETES AND SPOROZOITES (PFCELTOS), Ockenhouse4, Thomas L. Richie6, Meta Roestenberg7, Robert ADMINISTERED INTRAMUSCULARLY WITH GLA-SE W. Sauerwein7, Michele D. Spring4, Angela K. Talley8, Vasee S. ADJUVANT IN HEALTHY, MALARIA-NAÏVE ADULTS Moorthy9 Jessica J. Cowden1, Elke S. Bergmann-Leitner1, Susan Biggs- 1Howard Hughes Medical Institute/Center for Vaccine Development, Cicatelli1, Jason A. Regules1, Kristopher Paolino1, James E. Moon1, University of Maryland School of Medicine, Baltimore, MD, United States, Patrick Twomey1, James F. Cummings1, April Kathcart1, Edwin 2The Jenner Institute, University of Oxford, Oxford, United Kingdom, 3U.S. Kamau1, Alexander K. Kayatani1, Jack Komisar1, Jittawadee R. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Murphy1, Steve Reed2, Anna Marie Beckmann2, Derek Carter2, Spring, MD, United States, 4U.S. Military Malaria Vaccine Program, Walter Lorraine Soisson3, Randy Howard2, Carter Diggs3, Evelina Angov1, Reed Army Institute of Research, Silver Spring, MD, United States, 5Center Christian F. Ockenhouse1 for Vaccine Development, University of Maryland School of Medicine, 6 1Walter Reed Army Institute of Research, Silver Spring, MD, United States, Baltimore, MD, United States, U.S. Military Malaria Vaccine Program, 7 2Infectious Disease Research Institute, Seattle, WA, United States, 3United Naval Medical Research Center, Baltimore, MD, United States, Radboud States Agency for International Development, Washington, DC,