TY - JOUR
T1 - Salmonella Typhi outer membrane protein STIV is a potential candidate for vaccine development against typhoid and paratyphoid fever
AU - Das, Sayan
AU - Chowdhury, Rimi
AU - Pal, Ananda
AU - Okamoto, Keinosuke
AU - Das, Santasabuj
N1 - Funding Information:
This work was supported by grants from the Science and Engineering Research Board , Government of India (Grant no: EMR/2016/003283 ) and The Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) from Ministry of Education, Culture, Sport, Science & Technology in Japan , and Japan Agency for Medical Research and Development (AMED) (Grant no: JP18fm0108002 ).
Funding Information:
This work was supported by grants from the Science and Engineering Research Board, Government of India (Grant no: EMR/2016/003283) and The Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) from Ministry of Education, Culture, Sport, Science & Technology in Japan, and Japan Agency for Medical Research and Development (AMED) (Grant no: JP18fm0108002).
Publisher Copyright:
© 2019 Elsevier GmbH
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - Cell mediated immune response
KW - Humoral immune response
KW - Paratyphoid
KW - STIV
KW - Salmonella enterica serovar Paratyphi
KW - Salmonella enterica serovar Typhi
KW - Subunit vaccine
KW - Typhoid
UR - http://www.scopus.com/inward/record.url?scp=85063661567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063661567&partnerID=8YFLogxK
U2 - 10.1016/j.imbio.2019.02.011
DO - 10.1016/j.imbio.2019.02.011
M3 - Article
C2 - 30952553
AN - SCOPUS:85063661567
VL - 224
SP - 371
EP - 382
JO - Immunobiology
JF - Immunobiology
SN - 0171-2985
IS - 3
ER -