Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Nontyphoidal Salmonella (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 attenuated Salmonella typhimurium vaccine 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-type S. typhimurium strain 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-type S. typhimurium induces 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-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques.

Original languageEnglish (US)
Pages (from-to)5879-5888
Number of pages10
JournalVaccine
Volume31
Issue number49
DOIs
StatePublished - Dec 2 2013
Externally publishedYes

Fingerprint

Salmonella Vaccines
Simian immunodeficiency virus
Simian Immunodeficiency Virus
Salmonella typhimurium
Salmonella Typhimurium
Primates
mouth
live vaccines
vaccines
Safety
Attenuated Vaccines
Macaca mulatta
Salmonella
histopathology
Permeability
permeability
Vaccines
immunocompromised population
Neutrophil Infiltration
Africa South of the Sahara

Keywords

  • Human immunodeficiency virus
  • Live oral vaccine
  • Nonhuman primates
  • Nontyphoidal Salmonella
  • Simian immunodeficiency virus

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Ault, A., Tennant, S. M., Gorres, J. P., Eckhaus, M., Sandler, N. G., Roque, A., ... Rao, S. S. (2013). Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates. Vaccine, 31(49), 5879-5888. https://doi.org/10.1016/j.vaccine.2013.09.041

Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates. / 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.

In: Vaccine, Vol. 31, No. 49, 02.12.2013, p. 5879-5888.

Research output: Contribution to journalArticle

Ault, A, Tennant, SM, Gorres, JP, Eckhaus, M, Sandler, NG, Roque, A, Livio, S, Bao, S, Foulds, KE, Kao, SF, Roederer, M, Schmidlein, P, Boyd, MA, Pasetti, MF, Douek, DC, Estes, JD, Nabel, GJ, Levine, MM & Rao, SS 2013, 'Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates', Vaccine, vol. 31, no. 49, pp. 5879-5888. https://doi.org/10.1016/j.vaccine.2013.09.041
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. / Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates. In: Vaccine. 2013 ; Vol. 31, No. 49. pp. 5879-5888.
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