Venkatesan M.M.,U.S. Army |
van de Verg L.L.,Enteric Vaccine Initiative
Human Vaccines and Immunotherapeutics | Year: 2015
Diarrheal diseases remain a leading cause of global childhood mortality and morbidity. Several recent epidemiological studies highlight the rate of diarrheal diseases in different parts of the world and draw attention to the impact on childhood growth and survival. Despite the well-documented global burden of diarrheal diseases, currently there are no combination diarrheal vaccines, only licensed vaccines for rotavirus and cholera, and Salmonella typhi-based vaccines for typhoid fever. The recognition of the impact of diarrheal episodes on infant growth, as seen in resource-poor countries, has spurred action from governmental and non-governmental agencies to accelerate research toward affordable and effective vaccines against diarrheal diseases. Both travelers and children in endemic countries will benefit from a combination diarrheal vaccine, but it can be argued that the greater proportion of any positive impact will be on the public health status of the latter. The history of combination pediatric vaccines indicate that monovalent or single disease vaccines are typically licensed first prior to formulation in a combination vaccine, and that the combinations themselves undergo periodic revision in response to need for improvement in safety or potential for wider coverage of important pediatric pathogens. Nevertheless combination pediatric vaccines have proven to be an effective tool in limiting or eradicating communicable childhood diseases worldwide. The landscape of diarrheal vaccine candidates indicates that there now several in active development that offer options for potential testing of combinations to combat those bacterial and viral pathogens responsible for the heaviest disease burden—rotavirus, ETEC, Shigella, Campylobacter, V. cholera and Salmonella. © 2015, Taylor and Francis Inc, All Rights Reserved. .
Kaminski R.W.,U.S. Army |
Wu M.,U.S. Army |
Turbyfill K.R.,U.S. Army |
Clarkson K.,U.S. Army |
And 5 more authors.
Clinical and Vaccine Immunology | Year: 2014
Studies were undertaken to manufacture a multivalent Shigella inactivated whole-cell vaccine that is safe, effective, and inexpensive. By using several formalin concentrations, temperatures, and incubation periods, an optimized set of inactivation conditions was established for Shigella flexneri 2a, S. sonnei, and S. flexneri 3a to produce inactivated whole cells expressing a full repertoire of Ipa proteins and lipopolysaccharide (LPS). The inactivation conditions selected were treatment with 0.2% formalin (S. flexneri 2a and 3a) or 0.6% formalin (S. sonnei) for 48 h at 25°C. Vaccine formulations prepared under different inactivation conditions, in different doses (10E5, 10E7, and 10E9 cells), and with or without the inclusion of double-mutant heat-labile toxin (dmLT) were evaluated in mice. Two intranasal immunizations with ≥10E7 inactivated whole cells resulted in high levels of anti-Invaplex and moderate levels of LPS-specific IgG and IgA in serum and in lung and intestinal wash samples. Addition of dmLT to the vaccine formulations did not significantly enhance humoral immunogenicity. Minimal humoral responses for IpaB, IpaC, or IpaD were detected after immunization with inactivated whole Shigella cells regardless of the vaccine inactivation conditions. In guinea pigs, monovalent formulations of S. flexneri 2a of 3a or S. sonnei consisting of 10E8, 10E9, or 10E10 cells were protective in a keratoconjunctivitis assay. A trivalent formulation provided protection against all three serotypes (S. flexneri 2a, P = 0.018; S. flexneri 3a, P = 0.04; S. sonnei, P < 0.0001). The inactivated Shigella whole-cell vaccine approach incorporates an uncomplicated manufacturing process that is compatible with multivalency and the future development of a broadly protective Shigella vaccine. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Steele D.,Rotavirus Vaccine Program |
Riddle M.,U.S. Navy |
Van De Verg L.,Enteric Vaccine Initiative |
Bourgeois L.,Enteric Vaccine Initiative
Expert Review of Vaccines | Year: 2012
The 6th Vaccines for Enteric Diseases Symposium was held in Cannes, France, on 14-16 September 2011, drawing approximately 200 vaccine developers, academics and public health experts globally. Infectious diarrhea is a worldwide problem with high mortality and morbidity, particularly among children in the developing world. The WHO estimated approximately 8.8 million deaths in 2008 in young children aged 1-59 months, of which almost 2 million could be attributed to diarrheal illnesses - more than malaria, HIV/AIDS and TB combined. New breakthroughs in vaccine development, early clinical trials for the enterotoxigenic Escherichia coli, Shigella, noroviruses and conjugate typhoid vaccines, and updates on the implementation of rotavirus, cholera and typhoid vaccines were reported. © 2012 Expert Reviews Ltd.