Cholera immunity and development and use of oral cholera vaccines for disease control

• The development of oral cholera vaccines (OCVs) is a good example of how basic research can generate new knowledge that can be translated into a life-saving medical product. The key mechanisms of disease and immunity in cholera, which allowed outlining the principles for the first effective OCV, the inactivated whole cell/B subunit (WC-BS) OCV, later to be licensed as Dukoral, were defined already in the 1970s. Cholera was identified as an archetype for noninvasive, enterotoxin-mediated infectious diarrheal diseases in which immune protection is mediated largely by locally produced secretory immunoglobulin A (SIgA) antibodies interfering with bacterial attachment and colonization and/or preventing toxin binding and action in the intestine. These antibodies are directed primarily against the cell wall lipopolysaccharide (LPS) and cholera toxin B subunit (CTB), respectively. Since the intestinal SIgA responses in cholera lasts for only approximately 6-9 months, the continued protection for over 2-3 more years seen after infection or vaccination depends on mucosal immunological memory with a duration of more than 10 years, allowing a rapid SIgA antibacterial and antitoxic anamnestic response upon renewed pathogen exposure. Serum vibriocidal antibodies, although often correlating with adaptive immune protection, are only a proxy for the intestinal SIgA immune status. After Dukoral, which was internationally licensed in 1993, both inactivated and live, genetically attenuated OCVs have been developed. Inactivated OCVs have had the greatest success in achieving licensure and international acceptance. Three WHO-prequalified OCVs-Dukoral, Shanchol, and Euvichol-are currently available and differ mainly in that, in addition to several killed whole cell components shared with the other OCVs, the Dukoral OCV contains CTB. More than 15 large field trials have consistently shown that the described inactivated OCVs are quite safe and provide 60%-70% specific immune protection for at least 3 years. In addition, they confer significant “herd protection,” which further increases their total impact for reducing (or even eliminating) cholera in vaccinated communities. OCVs are now a cornerstone of a global initiative, “Ending Cholera-A Global Roadmap to 2030,” which was launched in October 2017 by the World Health Organization’s Global Task Force for Cholera Control together with more than 50 other signatories, with the stated goal of reducing cholera deaths by at least 90% by 2030. © 2020 Elsevier Inc. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

Cholera

Immune response

Mucosal immunity

Oral vaccine

Publikations- och innehållstyp

vet (ämneskategori)

kap (ämneskategori)