Parenteral Vaccination with a Cholera Conjugate Vaccine Boosts Vibriocidal and Anti-OSP Responses in Mice Previously Immunized with an Oral Cholera Vaccine

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  • 1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts;
  • 2 icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh;
  • 3 Department of Medicine, Harvard Medical School, Boston, Massachusetts;
  • 4 Department of Pediatrics, Harvard Medical School, Boston, Massachusetts;
  • 5 Division of Global Health, MassGeneral Hospital for Children, Boston, Massachusetts;
  • 6 NIDDK, LBC, National Institutes of Health, Bethesda, Maryland;
  • 7 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

Oral cholera vaccination protects against cholera; however, responses in young children are low and of short duration. The best current correlates of protection against cholera target Vibrio cholerae O-specific polysaccharide (anti-OSP), including vibriocidal responses. A cholera conjugate vaccine has been developed that induces anti-OSP immune responses, including memory B-cell responses. To address whether cholera conjugate vaccine would boost immune responses following oral cholera vaccination, we immunized mice with oral cholera vaccine Inaba CVD 103-HgR or buffer only (placebo) on day 0, followed by parenteral boosting immunizations on days 14, 42, and 70 with cholera conjugate vaccine Inaba OSP: recombinant tetanus toxoid heavy chain fragment or PBS/placebo. Compared with responses in mice immunized with oral vaccine alone or intramuscular cholera conjugate vaccine alone, mice receiving combination vaccination developed significantly higher vibriocidal, IgM OSP-specific serum responses and OSP-specific IgM memory B-cell responses. A combined vaccination approach, which includes oral cholera vaccination followed by parenteral cholera conjugate vaccine boosting, results in increased immune responses that have been associated with protection against cholera. These results suggest that such an approach should be evaluated in humans.

Author Notes

Address correspondence to Aklima Akter, icddr,b, 68, Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. E-mails: aklima17@gmail.com or akter.aklima@icddrb.org

Disclosure: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Financial support: This research was supported through programs funded by the NIH, including the National Institute of Allergy and Infectious Diseases (U01 AI106878 [E. T. R. and F. Q.], and AI137164 [R. C. C. and J. B. H.]), the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [A. A., R. B., T. R. B., and F. Q.]), Emerging Global Fellowship Award TW010362 [T. R. B.], and the Intramural Research Program of the NIH and NIDDK (P. X. and P. K.).

Authors’ Addresses: Aklima Akter, Taufiqur R. Bhuiyan, Rajib Biswas, and Firdausi Qadri, icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh, E-mails: akter.aklima@icddrb.org, taufiqur@icddrb.org, rajib@icddrb.org, and fqadri@icddrb.org. Meagan Kelly, Richelle Charles, Jason B. Harris, Stephen B. Calderwood, Edward T. Ryan, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, E-mails: mbufano@mgh.harvard.edu, rcharles@mgh.harvard.edu, jbharris@mgh.harvard.edu, scalderwood@mgh.harvard.edu, and etryan@mgh.harvard.edu. Peng Xu and Pavol Kovác, NIDDK, LBC, National Institutes of Health, Bethesda, MD, E-mails: peng.xu@nih.gov and kovac@niddk.nih.gov.

These authors contributed equally to this work.

These authors contributed equally to this work.

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