Significance of Vi Negative Isolates of Salmonella Enterica Serovar Typhi

  • Abdul HaqueEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1052)


Typhoid is a major global disease. The causative agent, Salmonella enterica serovar Typhi (S. Typhi) has a capsular antigen called Vi antigen which is traditionally considered to be the main cause of virulence. All the current vaccines are based on Vi antigen. However, the realization of the fact that there are S. Typhi strains which lack Vi antigen but still exist naturally and can cause disease has stirred great scientific interest. It is also interesting to note that their relative prevalence is affected by climatic conditions. Now it is established that Vi positive and Vi negative S. Typhi have different modes of pathogenesis; and as recent studies suggest, different structure of polysaccharide antigens. This means that current vaccines are not effective against a significant number of S. Typhi strains which not only affect the success of vaccination programs but also help in rapid emergence of Vi negative S. Typhi due to natural selection. The focus should be on vaccines based on antigens which are universally present in all S. Typhi. One such candidate is O-specific polysaccharides (OSPs). Successful attempts have been made to prepare conjugate vaccines based on OSPs.


Typhoid OSP antigen Conjugate vaccines 


  1. 1.
    Crump JA, Luby SP, Mintz ED (2004) The global burden of typhoid fever. Bull W H O 82:346–353PubMedPubMedCentralGoogle Scholar
  2. 2.
    Capoor MR, Nair D (2010) Quinolone and cephalosporin resistance in enteric Fever. J Glob Infect Dis 2:258–262CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    WHO 6th International conference on typhoid fever and other salmonellosis (2006) World Health Organization (Reference type: Pamphlet), GenevaGoogle Scholar
  4. 4.
    Baker S, Dougan G (2007) The Genome of Salmonella enterica serovar typhi. Clin Infect Dis 45 (Supplement 1): S29–S33. Scholar
  5. 5.
    Felix A, Pitt RM (1934) Notes on the Vi antigen of bacillus typhosus. J Path Bact 38:409CrossRefGoogle Scholar
  6. 6.
    Wang JC, Noriega FR, Galen JE, Barry E, Levine MM (2000) Constitutive expression of the Vi polysaccharide capsular antigen in attenuated Salmonella enterica serovar typhi oral vaccine strain CVD 909. Infect Immun 68:4647–4652CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bueno SM, Santiviago CA, Murillo AA, Fuentes JA, Trombert AN et al (2004) Precise excision of the large pathogenicity Island, SPI7, in Salmonella enterica serovar typhi. J Bacteriol 186:3202–3213CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nair S, Alokam S, Kothapalli S, Porwollik S, Proctor E et al (2004) Salmonella enterica serovar Typhi strains from which SPI7, a 134-kilobase Island with genes for Vi exopolysaccharide and other functions, has been deleted. J Bacteriol 186:3214–3223CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Baker S, Sarwar Y, Aziz H, Haque A, Ali A et al (2005) Detection of Vi-Negative Salmonella enterica serovar typhi in the peripheral blood of patients with typhoid fever in the Faisalabad region of Pakistan. J Clinc Microbiol 43:4418–4425CrossRefGoogle Scholar
  10. 10.
    Santander MJ, Roland KL, Curtiss RIII (2008) Regulation of Vi capsular polysaccharide synthesis in Salmonella enteric serotype typhi. J Infect Develop Count 2:412–420Google Scholar
  11. 11.
    Kolyva S, Waxin H, Popoff MY (1992) The Vi antigen of Salmonella typhi: molecular analysis of the viaBlocus. J Gen Microbiol 138:297–304CrossRefPubMedGoogle Scholar
  12. 12.
    Liston SD, Ovchinnikova OG, Whitfield C (2016) Unique lipid anchor attaches Vi antigen capsule to the surface of Salmonella enterica serovar Typhi. PNAS 113:6719–6724CrossRefPubMedGoogle Scholar
  13. 13.
    Saha MR, Ramamurthy T, Dutta P, Mitra U (2000) Emergence of Salmonella typhi Vi antigen-negative strains in an epidemic of multidrug-resistant typhoid fever cases in Calcutta, India. Natl Med J India 13:164PubMedGoogle Scholar
  14. 14.
    Tully JG, Currie JA (1962) Vi-negative strains of salmonella typhosa: attempts to induce w-v reversion and the use of non-vi strains in evaluating typhoid vaccines. J Bacteriol 84:747–753PubMedPubMedCentralGoogle Scholar
  15. 15.
    Pickard D, Wain J, Baker S, Line A, Chohan S et al (2003) Composition, acquisition, and distribution of the Vi exopolysaccharide-encoding Salmonella enterica pathogenicity island SPI-7. J Bacteriol 185:5055–5065CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mehta G, Arya SC (2002) Capsular Vi polysaccharide antigen in Salmonella enteric serovar typhi isolates. J Clin Microbio l40:1127–1128CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Pulickal AS, Callaghan MJ, Kelly DF, Maskey M, Mahat S et al (2013) Prevalence and genetic analysis of phenotypically Vi- negative Salmonella typhi isolates in children from Kathmandu, Nepal. J Trop Pediatr 59:317–320CrossRefPubMedGoogle Scholar
  18. 18.
    Ali A, Haque A, Haque A, Sarwar Y, Mohsin M et al (2009) Multiplex PCR for differential diagnosis of emerging typhoidal pathogens directly from blood samples. Epidemiol Infect 137:102–107CrossRefPubMedGoogle Scholar
  19. 19.
    Maurya P, Gulati AK, Nath K (2010) Vi gene stability and SPI-7 in S. Typhi status of Vi gene, its expression and Salmonella Pathogenicity Island (SPI-7) in Salmonella Typhi in India. Southeast Asian J Trop Med Public Health 41:913–919PubMedGoogle Scholar
  20. 20.
    Wain J, House D, Bhutta Z, Zafar A, Baker S et al (2005) Vi antigen expression in Salmonella enterica serovar typhi clinical isolates from Pakistan. J Clin Microbiol 43:1158–1165CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sur D, Ochiai RL, Bhattacharya SK (2009) A cluster-randomized effectiveness trial of Vi typhoid vaccine in India. N Engl J Med 361:335–344CrossRefPubMedGoogle Scholar
  22. 22.
    Feachem GR (1980) Appropriate technology for water supply and sanitation. The World Bank, Directorate of Information and Public Affairs, Washington D.C 20433Google Scholar
  23. 23.
    Hart PJ, O’Shaughnessy CM, Siggins MK, Bobat S, Kingsley RA et al (2016) Differential killing of Salmonella enterica serovar typhi by antibodies targeting Vi and lipopolysaccharide O:9 Antigen. PLOS Scholar
  24. 24.
    Liaqat S, Sarwar Y, Ali A, Haque A (2015) Comparative growth analysis of capsulated (vi+) and acapsulated (vi-) Salmonella typhi isolates in human blood. EXCLI 14:213–219Google Scholar
  25. 25.
    Hirose K, Ezaki T, Miyake M, Li T, Khan AQ et al (1997) Survival of Vi-capsulated and Vi-deleted Salmonella typhi strains in cultured macrophage expressing different levels of CD14 antigen. FEMS Microbiol Lett 147(2):259–265CrossRefPubMedGoogle Scholar
  26. 26.
    Robbins JD, Robbins JB (1984) Reexamination of the protective role of the capsular polysaccharide (Vi antigen) of Salmonella typhi. J Infect Dis 150:436–449CrossRefPubMedGoogle Scholar
  27. 27.
    Lee FK, Morris C, Hackett J (2006) The Salmonella enteric serovar Typhi Vi capsule and self-association pili share controls on expression. FEMS Microbiol Lett 261:41–46CrossRefPubMedGoogle Scholar
  28. 28.
    Helena MB, Seth-Smith (2008) SPI-7: Salmonella’s Vi-encoding pathogenicity Island. J Infect Develop Count 2:267–271Google Scholar
  29. 29.
    Haque A (2009) Biofilm is not or poorly produced by Vi negative isolates of S. Typhi. The 7th international symposium on invasive salmonelloses, Kilifi, Kenya, 25–28th Jan 2009. Proceedings available on Accessed 07 June 2010
  30. 30.
    Arricau N, Ecobichon C, Hermant D, Duffey PS, Waxin H et al (1998) The RcsB–RcsC regulatory system of Salmonella typhi differentially modulates the expression of invasion proteins, flagellin and Vi antigen in response to osmolarity. Mol Microbiol 29:835–850CrossRefPubMedGoogle Scholar
  31. 31.
    Caroff M, Karibian D (2003) Structure of bacterial lipopolysaccharides. Carbohydr Res 338(23):2431–2447CrossRefPubMedGoogle Scholar
  32. 32.
    Robbins JB, Schneerson R (1990) Polysaccharide-protein conjugates: a new generation of vaccines. J Infect Dis 161:821–832CrossRefPubMedGoogle Scholar
  33. 33.
    Jones C (2005) Vaccines based on the cell surface carbohydrates of pathogenic bacteria. An Acad Bras Cienc 77:293–324CrossRefPubMedGoogle Scholar
  34. 34.
    Goldblatt D (1998) Recent developments in bacterial conjugate vaccines. J Med Microbiol 47:563–567CrossRefPubMedGoogle Scholar
  35. 35.
    Finn A (2004) Bacterial polysaccharide-protein conjugate vaccines. Br Med Bull 70:1–14CrossRefPubMedGoogle Scholar
  36. 36.
    Crump JA, Mintz ED (2010) Global trends in typhoid and paratyphoid Fever. Clin Infect Dis 50:241–246CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Kossaczka Z, Lin FY, Ho VA, Thuy NT, Van Bay P et al (1999) Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam. Infect Immun 67:5806–5810PubMedPubMedCentralGoogle Scholar
  38. 38.
    Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV et al (2001) The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N Engl J Med 344:1263–1269CrossRefPubMedGoogle Scholar
  39. 39.
    Ali A, Cui C, An SJ, Haque A, Carbis R (2012) Preparation of immunogenic conjugates of Salmonella enterica serovar typhi O-specific polysaccharides (OSP) with Diphtheria toxoid (DT). Hum Vaccin Immunother (Formely Human Vaccines) 8(2):1–5Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Postgraduate Research Laboratory, Health Sciences CampusThe University of FaisalabadFaisalabadPakistan

Personalised recommendations