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Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria. Here we characterize the circulating B cell repertoires of 45 RTS,S/AS01 vaccinees and discover monoclonal antibodies for development as potential therapeutics. We generated >28,000 antibody sequences and tested 481 antibodies for binding activity and 125 antibodies for antimalaria activity in vivo. Through these analyses we identified correlations suggesting that sequences in Plasmodium falciparumcircumsporozoite protein, the target antigen in RTS,S/AS01, may induce immunodominant antibody responses that limit more protective, but subdominant, responses. Using binding studies, mouse malaria models, biomanufacturing assessments and protein stability assays, we selected AB-000224 and AB-007088 for advancement as a clinical lead and backup. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO’s preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development.

We report a case of febrile Plasmodium falciparummalaria in a 36-year-old male patient occurring 14 years after immigration from and more than 12 months since a return visit to the endemic area. The critical need for awareness regarding late presentations of P. falciparumis discussed.

Vibrio choleraeis a pathogen predominantly appreciated for its potential to produce life-threatening watery diarrhea, usually without invasive disease. However, nonepidemic forms, which are present worldwide, may have a severe invasive presentation, especially among those with liver disease or other immunocompromised states. We present a case of invasive infection (pulmonary, wound, and bacteremia) by nonepidemic V. cholerae, in a soldier that sustained burn injury in Iraq. Multiple factors, to include burn injury and water exposure, likely contributed to this presentation. A brief discussion of the pertinent literature is included.

ABSTRACTCommunity-associated methicillin-resistant Staphylococcus aureus(CA-MRSA) is an emerging pathogen that primarily manifests as uncomplicated skin and soft tissue infections. We conducted a cluster randomized, double-blind, placebo-controlled trial to determine whether targeted intranasal mupirocin therapy in CA-MRSA-colonized soldiers could prevent infection in the treated individual and prevent new colonization and infection within their study groups. We screened 3,447 soldiers comprising 14 training classes for CA-MRSA colonization from January to December 2005. Each training class was randomized to either the mupirocin or placebo study group, and the participants identified as CA-MRSA colonized were treated with either mupirocin or placebo. All participants underwent repeat screening after 8 to 10 weeks and were monitored for 16 weeks for development of infection. Of 3,447 participants screened, 134 (3.9%) were initially colonized with CA-MRSA. Five of 65 (7.7%; 95% confidence interval [95% CI], 4.0% to 11.4%) placebo-treated participants and 7 of 66 (10.6%; 95% CI, 7.9% to 13.3%) mupirocin-treated participants developed infections; the difference in the infection rate of the placebo- and mupirocin-treated groups was −2.9% (95% CI, −7.5% to 1.7%). Of those not initially colonized with CA-MRSA, 63 of 1,459 (4.3%; 95% CI, 2.7% to 5.9%) of the placebo group and 56 of 1,607 (3.5%; 95% CI, 2.6% to 5.2%) of the mupirocin group developed infections; the difference in the infection rate of the placebo and mupirocin groups was 0.8% (95% CI, −1.0% to 2.7%). Of 3,447 participants, 3,066 (89%) were available for the second sampling and completed follow-up. New CA-MRSA colonization occurred in 24 of 1,459 (1.6%; 95% CI, 0.05% to 2.8%) of the placebo group participants and 23 of 1,607 (1.4%; 95% CI, 0.05% to 2.3%) of the mupirocin group participants; the difference in the infection rate of the placebo and mupirocin groups was 0.2% (95% CI, −1.3% to 1.7%). Despite CA-MRSA eradication in colonized participants, this study showed no decrease in infections in either the mupirocin-treated individuals or within their study group. Furthermore, CA-MRSA eradication did not prevent new colonization within the study group.

Seroepidemiological studies on the prevalence of antibodies to malaria antigens are primarily conducted on individuals from regions of endemicity. It is therefore difficult to accurately correlate the antibody responses to the timing and number of prior malaria infections.

Immunological data could be used to demonstrate Ebola vaccine efficacy.