Summit proceedings: Biomedical countermeasure development for emerging vector-borne viral diseases.

Emerging and re-emerging infectious diseases are an expanding global threat to public health, security, and economies. Increasing populations, urbanization, deforestation, climate change, anti-vaccination movements, war, and international travel are some of the contributing factors to this trend. The recent Ebola, MERS-CoV, and Zika outbreaks demonstrated we are insufficiently prepared to respond with proven safe and effective countermeasures (i.

Use of Bibliometric Analysis to Assess the Scientific Productivity and Impact of the Global Emerging Infections Surveillance and Response System Program, 2006-2012.

Background: Scientific publication in academic literature is a key venue in which the U.S. Department of Defense's Global Emerging Infections Surveillance and Response System (GEIS) program disseminates infectious disease surveillance data.

Novel hemagglutinin nanoparticle influenza vaccine with Matrix-M™ adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted A(H3N2) subtypes.

Influenza viruses frequently acquire mutations undergoing antigenic drift necessitating annual evaluation of vaccine strains. Highly conserved epitopes have been identified in the hemagglutinin (HA) head and stem regions, however, current influenza vaccines induce only limited responses to these conserved sites. Here, we describe a novel seasonal recombinant HA nanoparticle influenza vaccine (NIV) formulated with a saponin-based adjuvant, Matrix-M™.

Clostridium difficile chimeric toxin receptor binding domain vaccine induced protection against different strains in active and passive challenge models.

Clostridium difficile is the number one cause of nosocomial antibiotic-associated diarrhea in developed countries. Historically, pathogenesis was attributed two homologous glucosylating toxins, toxin-A (TcdA) and toxin-B (TcdB). Over the past decade, however, highly virulent epidemic strains of C.

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

Background: A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.

Methods: We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B.

Respiratory Infections in the U.S. Military: Recent Experience and Control.

This comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures.

Evaluation of the certificate in emerging infectious disease research and the certificate in one health training programs, University of Florida.

In developing countries, public health professionals and scientists need targeted training and practical skills to respond to global emerging infectious disease threats. The Certificate in Emerging Infectious Disease Research was developed in 2008 to aid such professionals to respond to complex emerging disease problems. The short-course was modified slightly in 2013 and renamed the Certificate in One Health.

The state of antimicrobial resistance surveillance in the military health system: a review of improvements made in the last 10 years and remaining surveillance gaps.

During a military public health laboratory symposium held in 1999, concerns were raised that the military health system lacked a standardized antimicrobial resistance (AMR) surveillance system that allowed comparison of data across sites, investigation of trends, and understanding of resistance mechanisms. The purpose of this review was to assess if current AMR activities in the military health system have addressed the aforementioned gaps. It was determined that much progress has already been made within the Department of Defense with respect to monitoring and understanding AMR through initiatives such as the Antimicrobial Resistance Monitoring and Research Program-a strong Department of Defense-wide surveillance program.

Strengthening malaria prevention and control: integrating West African militaries' malaria control efforts. The inaugural meeting of the West African Malaria Task Force, April 24-26, 2013, Accra, Ghana.

From April 24 to 26, 2013, the Armed Forces Health Surveillance Center and the U.S. Africa Command cosponsored the inaugural meeting of the West Africa Malaria Task Force in Accra, Ghana.

Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1 dose-escalation study in healthy adults.

Background: Novel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al.

Detection of qacA/B in clinical isolates of methicillin-resistant Staphylococcus aureus from a regional healthcare network in the eastern United States.

We describe the clinical, microbiologic, and molecular features of the first series of qacA/B-containing strains of methicillin-resistant Staphylococcus aureus from infected US patients. All qac-carrying strains were clonally diverse, and qacA strains exhibited increased tolerance to chlorhexidine as measured by minimum inhibitory concentrations, minimum bactericidal concentrations, and postexposure colony counts.

The RTS,S vaccine candidate for malaria.

Malaria continues to be a worldwide leading cause of morbidity and mortality, and the development of an effective malaria vaccine remains a research imperative. Of the multiple approaches that have been pursued, the RTS,S/AS01 vaccine candidate represents the most developed and clinically validated malaria vaccine formulation. Throughout its development, increasingly more effective adjuvants have been key in improving the potency of the vaccine.

Plasmodium falciparum infection during suppressive prophylaxis with mefloquine does not induce an antibody response to merozoite surface protein-1(42).

A sensitive biomarker of malaria infection would obviate the need for placebo control arms in clinical trials of malaria prophylactic drugs. Antibodies to the 42-kDa fragment of merozoite surface protein-1 (MSP1(42)) have been identified as a potential marker of malaria exposure in individuals receiving prophylaxis with mefloquine. We conducted an open-label trial to determine the sensitivity of seroconversion to MSP1(42), defined as a fourfold rise in enzyme-linked immunosorbant assay (ELISA) titer, among 23 malaria naïve volunteers receiving mefloquine prophylaxis and 6 controls after Plasmodium falciparum sporozoite challenge.

Recombinant Liver Stage Antigen-1 (LSA-1) formulated with AS01 or AS02 is safe, elicits high titer antibody and induces IFN-gamma/IL-2 CD4+ T cells but does not protect against experimental Plasmodium falciparum infection.

Plasmodium falciparum Liver Stage Antigen 1 (LSA-1) is a pre-erythrocytic stage antigen. Our LSA-1 vaccine candidate is a recombinant protein with full-length C- and N-terminal flanking domains and two of the 17 amino acid repeats from the central repeat region termed "LSA-NRC." We describe the first Phase I/II study of this recombinant LSA-NRC protein formulated with either the AS01 or AS02 adjuvant system.

Evaluation of RTS,S/AS02A and RTS,S/AS01B in adults in a high malaria transmission area.

Background: This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.

Methodology: A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006.

Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection.

Background: To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS,S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals).

Methods: In a double-blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later.

Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A.

Background: This Phase 1/2a study evaluated the safety, immunogenicity, and efficacy of an experimental malaria vaccine comprised of the recombinant Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the 3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems.

Methodology/principal Findings: After a preliminary safety evaluation of low dose AMA-1/AS01B (10 microg/0.5 mL) in 5 adults, 30 malaria-naïve adults were randomly allocated to receive full dose (50 microg/0.

Phase 2a trial of 0, 1, and 3 month and 0, 7, and 28 day immunization schedules of malaria vaccine RTS,S/AS02 in malaria-naïve adults at the Walter Reed Army Institute of Research.

Background: Immunization with RTS,S/AS02 consistently protects some vaccinees against malaria infection in experimental challenges and in field trials. A brief immunization schedule against falciparum malaria would be compatible with the Expanded Programme on Immunization, or in combination with other prevention measures, interrupt epidemic malaria or protect individuals upon sudden travel to an endemic area.

Methods: We conducted an open label, Phase 2a trial of two different full dose schedules of RTS,S/AS02 in 40 healthy malaria-naïve adults.

Persistence of vaccinia at the site of smallpox vaccination.

Persistence of vaccinia at vaccination sites may help determine the risk associated with secondary transmission. Culture, PCR, and antigen detection were performed on serial vaccination site swab specimens. On day 21 after vaccination, 37% of volunteers were culture positive, most of whom had received vaccine for the first time.

Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naïve adults at the Walter Reed Army Institute of Research.

We report the first safety and immunogenicity trial of the Plasmodium falciparum vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the AS02A adjuvant.

Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in presymptomatic and clinically apparent malaria.

Using genome-wide expression profiles from persons either experimentally challenged with malaria-infected mosquitoes or naturally infected with Plasmodium falciparum malaria, we present details of the transcriptional changes that occur with infection and that either are commonly shared between subjects with presymptomatic and clinically apparent malaria or distinguish these two groups. Toll-like receptor signaling through NF-kappaB pathways was significantly upregulated in both groups, as were downstream genes that function in phagocytosis and inflammation, including the cytokines tumor necrosis factor alpha, gamma interferon (IFN-gamma), and interleukin-1beta (IL-1beta). The molecular program derived from these signatures illuminates the closely orchestrated interactions that regulate gene expression by transcription factors such as IRF-1 in the IFN-gamma signal transduction pathway.

Cutaneous delayed-type hypersensitivity (DTH) in a multi-formulation comparator trial of the anti-falciparum malaria vaccine candidate RTS,S in rhesus macaques.

Background: Studies are underway to identify more immunogenic formulations of the existing anti-falciparum malaria vaccine RTS,S/AS02A. To supplement in vitro immunogenicity assays, cutaneous delayed-type hypersensitivity (DTH) may be a useful indicator of functional, cell-mediated immunogenicity.

Methods: Adult rhesus monkeys were immunized with saline or one of four RTS,S/adjuvant formulations: RTS,S/AS01B, RTS,S/AS02A-standard (current formulation), RTS,S/AS05 or RTS,S/AS06 at 0, 4, and 12 weeks.