J Korean Med Sci.  2014 Apr;29(4):494-501. 10.3346/jkms.2014.29.4.494.

Safety and Immunogenicity Assessment of an Oral Cholera Vaccine through Phase I Clinical Trial in Korea

• Baik YO
• Choi SK
• Kim JW
• Yang JS
• Kim IY
• Kim CW
• Hong JH

• KMID: 1774453
• DOI: http://doi.org/10.3346/jkms.2014.29.4.494

Abstract

The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).

Keyword

Oral Cholera Vaccine; Safety; Immunogenicity; Vibriocidal Assay, Seroconversion Rate

MeSH Terms

Administration, Oral
Adult
Antibodies, Bacterial/*blood/immunology
Antibody Formation
Cholera/*prevention & control
Cholera Vaccines/adverse effects/*immunology
Creatine Kinase/blood
Humans
Male
Republic of Korea
Toothache/etiology
Vibrio cholerae O1/immunology
Antibodies, Bacterial
Cholera Vaccines
Creatine Kinase

Figure

• 

  Fig. 1 Schedule for each subject.

• 

  Fig. 2 Scattered dot plots of geometric mean antibody titer (GMT) to O1 Inaba, O1 Ogawa and O139 after oral administration of two doses of study drug given in 2 weeks apart. Grey boxes, error bars, and symbols indicate geometric means, 95% confidence intervals, and subjects, respectively.

• 

  Fig. 3 Scattered dot plots of GMF-rise from baseline titer to V. cholerae O1 Inaba, O1 Ogawa, and O139 measured on D14 and D28. Grey boxes, error bars, and symbols indicate geometric means, 95% confidence intervals, and subjects, respectively. Horizontal line at 1 represents line of identity.

Reference

1. Cholera vaccines: WHO position paper. Wkly Epidemiol Rec. 2010; 85:117–128.

2. World Health Organization. Background pager on the integration of oral cholera vaccines into global cholera control programmes. Geneva: WHO;2009.

3. Vu DT, Hossain MM, Nguyen DS, Nguyen TH, Rao MR, Do GC, Naficy A, Nguyen TK, Acosta CJ, Deen JL, et al. Coverage and costs of mass immunization of an oral cholera vaccine in Vietnam. J Health Popul Nutr. 2003; 21:304–308.

4. Quick RE, Venczel LV, González O, Mintz ED, Highsmith AK, Espada A, Damiani E, Bean NH, De Hannover EH, Tauxe RV. Narrow-mouthed water storage vessels and in situ chlorination in a Bolivian community: a simple method to improve drinking water quality. Am J Trop Med Hyg. 1996; 54:511–516.

5. Kanungo S, Paisley A, Lopez AL, Bhattacharya M, Manna B, Kim DR, Han SH, Attridge S, Carbis R, Rao R, et al. Immune responses following one and two doses of the reformulated, bivalent, killed, whole-cell, oral cholera vaccine among adults and children in Kolkata, India: a randomized, placebo-controlled trial. Vaccine. 2009; 27:6887–6893.

6. Mahalanabis D, Lopez AL, Sur D, Deen J, Manna B, Kanungo S, von Seidlein L, Carbis R, Han SH, Shin SH, et al. A randomized, placebo-controlled trial of the bivalent killed, whole-cell, oral cholera vaccine in adults and children in a cholera endemic area in Kolkata, India. PLoS One. 2008; 3:e2323.

7. Sur D, Lopez AL, Kanungo S, Paisley A, Manna B, Ali M, Niyogi SK, Park JK, Sarkar B, Puri MK, et al. Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2009; 374:1694–1702.

8. Guidelines for the production and control of inactivated oral cholera vaccines: annex 3, WHO technical report. 2004. Series No. 924.

9. Anh DD, Canh do G, Lopez AL, Thiem VD, Long PT, Son NH, Deen J, von Seidlein L, Carbis R, Han SH, et al. Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults. Vaccine. 2007; 25:1149–1155.

10. Jertborn M, Svennerholm AM, Holmgren J. Saliva, breast milk, and serum antibody responses as indirect measures of intestinal immunity after oral cholera vaccination or natural disease. J Clin Microbiol. 1986; 24:203–209.

11. Attridge SR, Johansson C, Trach DD, Qadri F, Svennerholm AM. Sensitive microplate assay for detection of bactericidal antibodies to Vibrio cholerae O139. Clin Diagn Lab Immunol. 2002; 9:383–387.

12. Gotuzzo E, Butron B, Seas C, Penny M, Ruiz R, Losonsky G, Lanata CF, Wasserman SS, Salazar E, Kaper JB. Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels. Infect Immun. 1993; 61:3994–3997.

13. Taylor DN, Cárdenas V, Perez J, Puga R, Svennerholm AM. Safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit (WC/rCTB) cholera vaccine in Peruvian adults and children. Am J Trop Med Hyg. 1999; 61:869–873.

14. Qadri F, Svennerholm AM, Shamsuzzaman S, Bhuiyan TR, Harris JB, Ghosh AN, Nair GB, Weintraub A, Faruque SM, Ryan ET, et al. Reduction in capsular content and enhanced bacterial susceptibility to serum killing of Vibrio cholerae O139 associated with the 2002 cholera epidemic in Bangladesh. Infect Immun. 2005; 73:6577–6583.

15. Saha D, LaRocque RC, Khan AI, Harris JB, Begum YA, Akramuzzaman SM, Faruque AS, Ryan ET, Qadri F, Calderwood SB. Incomplete correlation of serum vibriocidal antibody titer with protection from Vibrio cholerae infection in urban Bangladesh. J Infect Dis. 2004; 189:2318–2322.

16. Chatterjee SN, Chaudhuri K. Lipopolysaccharides of Vibrio cholera: I. physical and chemical characterization. Biochim Biophys Acta. 2003; 1639:65–79.

17. Weintraub A, Widmalm G, Jansson PE, Jansson M, Hultenby K, Albert MJ. Vibrio cholerae O139 Bengal possesses a capsular polysaccharide which may confer increased virulence. Microb Pathog. 1994; 16:235–241.