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Immunobiology. 2019 May;224(3):371-382. doi: 10.1016/j.imbio.2019.02.011. Epub 2019 Mar 22.

Salmonella Typhi outer membrane protein STIV is a potential candidate for vaccine development against typhoid and paratyphoid fever.

Author information

1
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, P-33 Scheme-XM, C.I.T. Road, Beliaghata, Kolkata, 700010, India.
2
Collaborative Research Center of Okayama University for Infectious Diseases at Indian Council of Medical Research- National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India; Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
3
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, P-33 Scheme-XM, C.I.T. Road, Beliaghata, Kolkata, 700010, India. Electronic address: dasss@icmr.org.in.

Abstract

Enteric fever, caused by Salmonella enterica serovars, Typhi (S. Typhi) and Paratyphi (S. Paratyphi) is a major public health challenge for the developing nations. Globally, the disease affects ˜15-30 million individuals every year, resulting in >200,000 deaths. Multidrug-resistant S. Typhi H58 strain has emerged as the dominant circulating strain in a large part of the world and an extensively drug-resistant (XDR) subclade of the strain was recently reported. Many believe that vaccination of the susceptible populations is urgently needed and the best option to control the infection. However, the commercial live attenuated (Ty21a) vaccine is not recommended for children below six years of age while the Vi-polysaccharide-based vaccine has poor long-term efficacy against typhoid fever. Moreover, no vaccines are available against S. Paratyphi infection. Thus, a new formulation capable of providing long term protection against both the pathogens and safe for all age groups is immediately required. We show that recombinant, S. Typhi outer membrane protein STIV (rSTIV) is immunogenic in mice and elicits high serum titers of different immunoglobulin subtypes. STIV antibodies opsonize S. Typhi and S. Paratyphi A to promote antibody-dependent cellular cytotoxicity and complement-mediated lysis. Immunization with rSTIV also induces robust cell-mediated immunity, including antigen-specific T cell proliferation and cytotoxic T lymphocyte response. Finally, mice immunized with rSTIV are significantly protected against S. Typhi and S. Paratyphi A challenge, with reduced visceral bacterial load. Our results underscore the potential of rSTIV as a novel vaccine candidate for enteric fever.

KEYWORDS:

Cell mediated immune response; Humoral immune response; Paratyphoid; STIV; Salmonella enterica serovar Paratyphi; Salmonella enterica serovar Typhi; Subunit vaccine; Typhoid

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