Details

Autor(en) / Beteiligte

• Ault, Alida
• Tennant, Sharon M
• Gorres, J Patrick
• Eckhaus, Michael
• Sandler, Netanya G
• Roque, Annelys
• Livio, Sofie
• Bao, Saran
• Foulds, Kathryn E
• Kao, Shing-Fen
• Roederer, Mario
• Schmidlein, Patrick
• Boyd, Mary Adetinuke
• Pasetti, Marcela F
• Douek, Daniel C
• Estes, Jacob D
• Nabel, Gary J
• Levine, Myron M
• Rao, Srinivas S

Titel

Safety and tolerability of a live oralSalmonella typhimuriumvaccine candidate in SIV-infected nonhuman primates

Ist Teil von

• Vaccine, 2013-12, Vol.31 (49), p.5879

Ort / Verlag

Kidlington: Elsevier Limited

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• NontyphoidalSalmonella(NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuatedSalmonella typhimuriumvaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-typeS.typhimuriumstrain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-typeS. typhimuriuminduces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuatedS. typhimuriumstrain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques.