Research Article: Flexibility of Oral Cholera Vaccine Dosing—A Randomized Controlled Trial Measuring Immune Responses Following Alternative Vaccination Schedules in a Cholera Hyper-Endemic Zone

Date Published: March 12, 2015

Publisher: Public Library of Science

Author(s): Suman Kanungo, Sachin N. Desai, Ranjan Kumar Nandy, Mihir Kumar Bhattacharya, Deok Ryun Kim, Anuradha Sinha, Tanmay Mahapatra, Jae Seung Yang, Anna Lena Lopez, Byomkesh Manna, Barnali Bannerjee, Mohammad Ali, Mandeep Singh Dhingra, Ananga Mohan Chandra, John D. Clemens, Dipika Sur, Thomas F. Wierzba, Edward T. Ryan.

Abstract: BackgroundA bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response.Methodology/Principal FindingsIn this double blind randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55%) vs the 28 day interval (58%). Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%).Conclusions/SignificanceComparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.

Partial Text: As a disease of poverty and inequity, cholera is often prevalent in areas of compromised sanitation, overcrowded conditions, and poor quality of water supply. An increasing number of longer lasting outbreaks have dramatically impacted the least developed countries (LDCs), including those in Africa, South Asia, and the Hispaniola island region [1]. Living conditions in LDC populations often favor disease transmission and improvements can take a long time to achieve. In these settings, V. cholerae O1 can cause large, rapidly spreading severe outbreaks that cripple public health systems with already limited medical and financial resources. Many recent epidemics have occurred in highly susceptible and vulnerable populations (Haiti, Zimbabwe, Central and West Africa), where behavioral, social, and environmental factors, as well as lower background exposure to cholera have contributed to increased duration and severity of the outbreaks [2]. Effective interventions combining surveillance, treatment, and improving water, sanitation, and hygiene (WASH) measures are paramount. Vaccination can complement these preventive and control strategies in areas of endemic disease or areas at risk for outbreak [3]. Recently, a killed, bivalent oral cholera vaccine (OCV) has been prequalified and recommended for use by the WHO. Still, this OCV has not been widely implemented in endemic areas and its use is limited to areas with established or imminent outbreaks.

The results of our study support flexibility in dosing Shanchol in endemic settings, where strict schedules may be difficult to adhere to. As with any immunogenicity findings, vibriocidal antibodies do not truly reflect a protective response and, at best, are an indirect correlate of protection that is not absolute. While only a field trial can determine true effectiveness of altered dosing regimens, interpreting this data in light of the existing immunogenicity and clinical efficacy data in the same setting may provide a foundation for policy makers to ease implementation of OCV as part of a control strategy for cholera.



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