Scalable production and immunogenicity of a cholera conjugate vaccine
Year: 2021
Type: article
Abstract: There is a need to develop cholera vaccines that are protective in young children under 5 years of age, which induce long-term immunity, and which can be incorporated into the Expanded Programme of Immunization (EPI) in cholera-endemic countries. The degree of protection afforded by currently available oral cholera vaccines (OCV) to young children is significantly lower than that induced by vaccination of older vaccine recipients. Immune responses that protect against cholera target the O-specific polysaccharide (OSP) of Vibrio cholerae, and young children have poor immunological responses to bacterial polysaccharides, which are T cell independent antigens. To overcome this, we have developed a cholera conjugate vaccine (CCV) containing the OSP of V. cholerae O1, the main cause of endemic and epidemic cholera. Here, we describe production of CCV through a scalable manufacturing process and preclinical evaluation of immunogenicity in the presence and absence of aluminum phosphate (alum) as an adjuvant. The vaccine displays V. cholerae O1 Inaba OSP in sun-burst display via single point attachment of core oligosaccharide to a recombinant tetanus toxoid heavy chain fragment (rTTHc). Two different pilot-scale production batches of non-GMP CCV were manufactured and characterized in terms of physico-chemical properties and immunogenicity. In preclinical testing, the vaccine induced OSP- and lipopolysaccharide (LPS)-specific IgG and IgM responses, vibriocidal responses, memory B cell responses, and protection in a V. cholerae O1 challenge model. The addition of alum to the administered vaccine increased OSP-specific immune responses. These results support evaluation of CCV in humans.
Source: Vaccine
Authors: Suhi Jeon, Meagan Kelly, Jeesun Yun, Byungman Lee, Minchul Park, Yoonhee Whang, Chankyu Lee, Yuan-Di Halvorsen, Smriti Verma, Richelle C. Charles, Jason B. Harris, Stephen B. Calderwood, Daniel T. Leung, Taufiqur R. Bhuiyan, Firdausi Qadri, Mohammad Kamruzzaman, Somyoung Cho, Willie F. Vann, Peng Xu, Pavol Kováč, Ravi Ganapathy, Julia Lynch, Edward T. Ryan
Institutions: Massachusetts General Hospital, Harvard University, University of Utah, International Centre for Diarrhoeal Disease Research, International Vaccine Institute, Center for Biologics Evaluation and Research, United States Food and Drug Administration, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,950
Awards: G1510978416, O-Specific Polysaccharide Responses and Cholera, Antibody mediated protective immunity against cholera, G516757433, G6010259269, O-Specific Polysaccharide Responses and Cholera, Preclinical Toxicology Testing and IND application for a Novel Cholera Conjugate Vaccine, Humoral and adaptive immune responses study in Vibrio cholerae infection, G8951220445, O-Specific Polysaccharide Responses and Cholera, International research training program in vaccine development and public health
OpenAlex ID: W3208316892