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Objective To assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial In the Gambia. Methods Adults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants' comprehension of informed consent. This was done immediately after consent had been obtained (at day 0) and at subsequent follow-up visits (days 7,14,21 and 28).The acceptability and ease of use of the multimedia tool were assessed in focus groups. Findings On day 0, the median comprehension score in the intervention arm was 64% compared with 40% in the control arm (P=0.042). The difference remained significant at all follow-up visits. Poorer comprehension was independently associated with female sex (odds ratio, OR: 0.29; 95% confidence Interval, CI: 0.12-0.70) and residing in Jahaly rather than Basse province (OR: 0.33; 95% CI: 0.13-0.82). There was no significant independent association with educational level. The risk that a participant's comprehension score would drop to half of the initial value was lower in the intervention arm (hazard ratio 0.22,95% CI: 0.16-0.31). Overall, 70% (42/60) of focus group participants from the Intervention arm found the multimedia tool dear and easy to understand. Conclusion A multimedia informed consent tool significantly improved comprehension and retention of consent information by research participants with low levels of literacy. Objectif Evaluer l'efficacite d'un outil multimedia de consentement eclaire pour les adultes participant a un essai clinique en Gambie. Methodes Les adultes eligibles a la participation a un essai de traitement du paludisme (n=311) ont ete randomises pour le recuell des informations necessaires au consentement eclaire, au moyen d'un outil multimedia (branche d'intervention) ou bien de la procedure standard (branche temoin). Un questionnaire audio informatise a ete utilise pour evaluer la comprehension du consentement eclaire par les participants, immediatement apres l'obtention de ce consentement (jour 0) alnsi que lors des visites de suivi ulterleures (jours 7,14,21 et 28). L'acceptablllte et la facilite d'utillsatlon de cet outil multimedia ont ete evaluees dans des groupes de discussions. Resultats Au jour 0, le score median de comprehension dans la branche d'intervention etalt de 64% contre 40% dans la branche temoin (P=0,042). La difference est restee significative lors de toutes les visites de suivi. Les difficultes de comprehension etaient associees independamment au sexe feminin (rapport des cotes, RC: 0,29; intervalle de confiance de 95%, IC: 0,12-0,70) et au fait de resider dans la province de Jahaly plutot que dans celle de Basse (RC: 0,33; IC de 95%: 0,13-0,82). Aucune association independante significative avec le niveau d'education n'a ete observee. Le risque de voir le score de comprehension d'un participant baisser de moitie par rapport a sa valeur initiale etait plus faible dans la branche d'intervention (ratio de risque 0,22, IC de 95%: 0,16-0,31). Globalement, 70% (42/60) des participants du groupe de discussion de la branche d'intervention ont trouve l'outil multimedia clair et facile a comprendre. Conclusion L'outil multimedia de consentement eclaire a sensiblement ameliore la comprehension et la memorisation des informations sur le consentement par les participants a des recherches ayant un faible niveau d'alphabetisation. Objetivo Evaluar la eficacia de una herramienta multimedia para el consentimiento informado para los adultos que participan en un ensayo clinico en Gambia. Metodos Los adultos elegibles para ser incluidos en un ensayo de los tratamientos de la malaria (n = 311) fueron aleatorizados para recibir la informacion necesaria para el consentimiento informado mediante una herramienta multimedia (brazo de intervencion) o un procedimiento estandar (brazo de control). Se utilizo un cuestionario de audio electronico para evaluar la comprension de los participantes del consentimiento informado. Esto se realizo inmediatamente despues de la obtencion del consentimiento (el dia 0) y en las visitas de seguimiento posteriores (dias 7,14,21 y 28). La aceptacion y facilidad de uso de la herramienta multimedia se evaluo en grupos muestrales. Resultados En el dia 0, la puntuacion de comprension media en el brazo de intervencion fue del 64%, en comparacion con el 40% en el brazo de control (P = 0,042). La diferencia siguio siendo significativa en todas las visitas de seguimiento. La peor comprension se relaciono independientemente con el sexo femenino (cociente de posibilidades, CP: 0,29; 95% intervalo de confianza, IC: 0,12-0,70) y con los residentes en Jahaly en lugar de la provincia de Basse (CP: 0,33 (95% IC: 0,13-0,82). No hubo ninguna asociacion independiente significativa con el nivel educativo. El riesgo de que la puntuacion de comprension de un participante se redujese a la mitad de la puntuacion inicial era menor en el brazo de Intervencion (cociente de riesgos instantaneos 0,22,95% IC: 0,16-0,31). En terminos generales, el 70% (42/60) de los participantes del grupo muestral del brazo de intervencion consideraron que la herramienta multimedia era clara y facil de entender. Conclusion Una herramienta multimedia para el consentimiento informado mejoro considerablemente la comprension y retencion de la informacion consentida por los participantes en la investigacion con bajos niveles de alfabetizacion., Introduction Clinical trial participants in sub-Saharan Africa often have limited understanding of the study information provided during the informed consent process. Low literacy and the difficulty of presenting information in [...]

Abstract Since 2000, under the Fifth and subsequent Framework Programmes, the European Commission has funded research to spur the development of a malaria vaccine. This funding has contributed to the promotion of an integrated infrastructure consisting of European basic, applied and clinical scientists in academia and small and medium enterprises, together with partners in Africa. Research has added basic understanding of what is required of a malaria vaccine, allowing selected candidates to be prioritized and some to be moved forward into clinical trials. To end the health burden of malaria, and its economic and social impact on development, the international community has now essentially committed itself to the eventual eradication of malaria. Given the current tentative advances towards elimination or eradication of malaria in many endemic areas, malaria vaccines constitute an additional and almost certainly essential component of any strategic plan to interrupt transmission of malaria. However, funding for malaria vaccines has been substantially reduced in the Seventh Framework Programme compared with earlier Framework Programmes, and without further support the gains made by earlier European investment will be lost.

The article looks at a study regarding vaccination with the recombinant viral vectors chimpanzee adenovirus 63 and modified vaccinia Ankara encoding the malaria peptide sequence multiple epitope string and thrombospondin-related adhesion protein (ME-TRAP). It mentions antimalarials to clear parasitemia and conducted polymerase chain reaction (PCR) with the malaria parasite Plasmodium falciparum. It also mentions vaccination reduced the risk of infection.

Objective: To develop and psychometrically evaluate an audio digitised tool for assessment of comprehension of informed consent among low-literacy Gambian research participants. Setting: We conducted this study in the Gambia where a high illiteracy rate and absence of standardised writing formats of local languages pose major challenges for research participants to comprehend consent information. We developed a 34-item questionnaire to assess participants' comprehension of key elements of informed consent. The questionnaire was face validated and content validated by experienced researchers. To bypass the challenge of a lack of standardised writing formats, we audiorecorded the questionnaire in three major Gambian languages: Mandinka, Wolof and Fula. The questionnaire was further developed into an audio computer-assisted interview format. Participants: The digitised questionnaire was administered to 250 participants enrolled in two clinical trials in the urban and rural areas of the Gambia. One week after first administration, the questionnaire was readministered to half of the participants who were randomly selected. Participants were eligible if enrolled in the parent trials and could speak any of the three major Gambian languages. Outcome measure: The primary outcome measure was reliability and validity of the questionnaire. Results: Item reduction by factor analysis showed that 21 of the question items have strong factor loadings. These were retained along with five other items which were fundamental components of informed consent. The 26-item questionnaire has high internal consistency with a Cronbach's α of 0.73-0.79 and an intraclass correlation coefficient of 0.94 (95% CI 0.923 to 0.954). Hypotheses testing also showed that the questionnaire has a positive correlation with a similar questionnaire and discriminates between participants with and without education. Conclusions: We have developed a reliable and valid measure of comprehension of informed consent information for the Gambian context, which might be easily adapted to similar settings. This is a major step towards engendering comprehension of informed consent information among low-literacy participants. [ABSTRACT FROM AUTHOR]

Abstract: This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. [Copyright &y& Elsevier]

Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)-thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model. Methods and Findings A total of 372 Gambian men aged 15-45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, 22% to + 34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity. [ABSTRACT FROM AUTHOR]

Background: The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).Methods: In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian).Findings: Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 10(10) pu, 35 [38%] to 2·5 × 10(10) pu, 35 [38%] to 5 × 10(10) pu, and 11 [12%] to 1 × 10(11) pu) and 20 in the USA (ten [50%] to 1 × 10(10) pu and ten [50%] to 1 × 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 10(10) and two [2%] received 1 × 10(11) pu) and four (20%) of 20 in the USA (all received 1 × 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness.Interpretation: 1 × 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers).Funding: Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines., Methods: We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines., Results: The vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8 + T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly., Conclusion: Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations., Clinical Trial Registration: The clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8 + T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8 +  and CD4 + T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Malaria transmission is in decline in some parts of Africa, partly due to the scaling up of control measures. If the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. Studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen ME-TRAP (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge studies. More recently, a study in Kenyan adults, similar to that reported here, showed substantial efficacy against P. falciparum infection. One hundred and twenty healthy male volunteers, living in a malaria endemic area of Senegal were randomised to receive either the Chimpanzee adenovirus (ChAd63) ME-TRAP as prime vaccination, followed eight weeks later by modified vaccinia Ankara (MVA) also encoding ME-TRAP as booster, or two doses of anti-rabies vaccine as a comparator. Prior to follow-up, antimalarials were administered to clear parasitaemia and then participants were monitored by PCR for malaria infection for eight weeks. The primary endpoint was time-to-infection with P. falciparum malaria, determined by two consecutive positive PCR results. Secondary endpoints included adverse event reporting, measures of cellular and humoral immunogenicity and a meta-analysis of combined vaccine efficacy with the parallel study in Kenyan adults.We show that this pre-erythrocytic malaria vaccine is safe and induces significant immunogenicity, with a peak T-cell response at seven days after boosting of 932 Spot Forming Cells (SFC)/106 Peripheral Blood Mononuclear Cells(PBMC) compared to 57 SFC/ 106 PBMCs in the control group. However, a vaccine efficacy was not observed: 12 of 57 ME-TRAP vaccinees became PCR positive during the intensive monitoring period as compared to 13 of the 58 controls (P = 0.80). This trial confirms that vaccine efficacy against malaria infection in adults may be rapidly assessed using this efficient and cost-effective clinical trial design. Further efficacy evaluation of this vectored candidate vaccine approach in other malaria transmission settings and age-de-escalation into the main target age groups for a malaria vaccine is in progress., Competing Interests: We have the following interests. Adrian V.S. Hill is a named inventor on patent applications and patents on malaria vectored vaccines and immunisation regimes including the following (WO2008/122769, Adenoviral vector encoding malaria antigen; and WO 2008/122811 Novel adenovirus vectors). Egeruan Imoukhuede and Ines Petersen were employees of EVI at the time of the study, which supports the development and testing of malaria vaccines. Nicola Viebig is an employee of EVI and Odile Leroy is executive director of EVI. Authors from ReiThera (formerly Okairos) are employees of and/or shareholders in ReiThera, which is developing vectored vaccines for malaria and other diseases. Alfredo Nicosia was employed by ReiThera (formerly Okairos) at the time of the study. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity., Competing Interests: Statement The following authors have declared that no conflict of interest exists: MOA, CMB, ABT, AD, IN, YJJ, JUA, JNJ, SHH, NAA, CJD, RR, NKV, OL, AML. KLF, BK, PB, EBI, SBS, KB, KJE. AVSH is a named inventor on patent applications on malaria vectored vaccines and immunization regimens. Authors from ReiThera are employees of and/or shareholders in ReiThera, which is developing vectored vaccines for malaria and other diseases.

To induce a deployable level of efficacy, a successful malaria vaccine would likely benefit from both potent cellular and humoral immunity. These requirements are met by a heterologous prime-boost immunization strategy employing a chimpanzee adenovirus vector followed by modified vaccinia Ankara (MVA), both encoding the pre-erythrocytic malaria antigen ME-thrombospondin-related adhesive protein (TRAP), with high immunogenicity and significant efficacy in UK adults. We undertook two phase 1b open-label studies in adults in Kenya and The Gambia in areas of similar seasonal malaria transmission dynamics and have previously reported safety and basic immunogenicity data. We now report flow cytometry and additional interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) data characterizing pre-existing and induced cellular immunity as well as anti-TRAP IgG responses. T-cell responses induced by vaccination averaged 1,254 spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) across both trials and flow cytometry revealed cytokine production from both CD4(+) and CD8(+) T cells with the frequency of CD8(+) IFN-γ-secreting monofunctional T cells (previously shown to associate with vaccine efficacy) particularly high in Kenyan adults. Immunization with ChAd63 and MVA ME-TRAP induced strong cellular and humoral immune responses in adults living in two malaria-endemic regions of Africa. This prime-boost approach targeting the pre-erythrocytic stage of the malaria life-cycle is now being assessed for efficacy in a target population.

Prior to a chimpanzee adenovirus-based (ChAd63) malarial vaccine trial, sera were collected to assess ChAd63-specific neutralizing antibody titers in Banfora (Burkina Faso). The low neutralizing antibody titers reported in both adults and children (median titers, 139.1 and 35.0, respectively) are encouraging for the potential use of ChAd63 as a malarial vaccine vector., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI)., Methodology: We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns., Results: ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC)., Conclusions: ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted., Trial Registration: Pactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430.

The feasibility of using a sensitive polymerase chain reaction (PCR) to evaluate malaria vaccines in small group sizes was tested in 102 adult Gambian volunteers who received either the malaria vaccine regimen FP9 ME-TRAP/MVA ME-TRAP or rabies vaccine. All volunteers received the antimalarial drugs primaquine and Lapdap plus artesunate to eliminate malaria parasites. Volunteers in a further group received an additional single treatment with sulfadoxine-pyrimethamine (SP) to prevent new infections. There was substantially lower T-cell immunogenicity than in previous trials with this vaccine regimen and no protection against infection in the malaria vaccine group. Using the primary endpoint of 20 parasites per mL, no difference was found in the prevalence of low-level infections in volunteers who received SP compared with those who did not, indicating that SP did not reduce the incidence of very low-density infection. However, SP markedly reduced the incidence of higher density infections. These findings support the feasibility and potential of this approach to screen pre-erythrocytic vaccines for efficacy against infection in small numbers of vaccinees in endemic areas.