Name
Identification of maternal, genetic and medical factors that influence rotavirus vaccine efficacy in a large-scale clinical trial in Vietnamese infants
Presenter
Sarah Caddy, Baker Institute for Animal Health, Cornell University
Co-Author(s)
Sarah Caddy, Baker Institute for Animal Health, Cornell University, USA
Tom Lonergan, Baker Institute for Animal Health, Cornell University, USA
Benjamin Bai, Wellcome Sanger Institute, Hinxton, UK
Duy Pham Thanh, Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam
Maryam Ahmed, Baker Institute for Animal Health, Cornell University, USA
Nabila Dewar Binti, Baker Institute for Animal Health, Cornell University, USA
Tam Pham Thi Thanh, OUCRU, Ho Chi Minh City, Vietnam
Tran My Phuc, OUCRU, Ho Chi Minh City, Vietnam
Carl Anderson, Wellcome Sanger Institute, Hinxton, UK
Steven Baker, A*STAR Infectious Diseases Labs, Agency for Science, Technology and Research, Singapore
Abstract Category
Vaccines
Abstract
Rotavirus vaccines are often less than 50% effective in lower middle-income countries (LMIC). Multiple reasons for poor efficacy have been proposed, including maternal antibody interference, genetic or microbiome differences, and co-infections. A better understanding of which factors correlate with success or failure of seroconversion is essential to guide the development of future vaccine strategies.
To study factors affecting rotavirus vaccine efficacy in Vietnam, a single-arm interventional trial with the Rotarix vaccine was conducted. A total of 818 infants were recruited and vaccinated at 2 and 3 months of age. Serum was collected at each vaccination visit and at 6, 12 and 18 months of age. Baseline demographic and clinical data were collected, and whole genome sequencing was performed for every infant. Rotavirus-specific IgA titers were determined by ELISA at each timepoint to evaluate seroconversion. Rotavirus-specific IgG titers were determined in pre-vaccine samples to quantify maternal antibodies transferred across the placenta.
Only 42.5% infants seroconverted after the first vaccine dose, rising to 48.1% after the second dose, reinforcing the conclusion that vaccine efficacy in reduced in LMICs. Four key determinants were significantly associated with seroconversion; maternal antibody titer, secretor status, birth method, and vaccination with the oral polio vaccine 2 days after Rotarix administration. Our findings highlight the multiple challenges faced by use of current vaccines, and identify the factors that are essential to consider in development of new rotavirus vaccines.
To study factors affecting rotavirus vaccine efficacy in Vietnam, a single-arm interventional trial with the Rotarix vaccine was conducted. A total of 818 infants were recruited and vaccinated at 2 and 3 months of age. Serum was collected at each vaccination visit and at 6, 12 and 18 months of age. Baseline demographic and clinical data were collected, and whole genome sequencing was performed for every infant. Rotavirus-specific IgA titers were determined by ELISA at each timepoint to evaluate seroconversion. Rotavirus-specific IgG titers were determined in pre-vaccine samples to quantify maternal antibodies transferred across the placenta.
Only 42.5% infants seroconverted after the first vaccine dose, rising to 48.1% after the second dose, reinforcing the conclusion that vaccine efficacy in reduced in LMICs. Four key determinants were significantly associated with seroconversion; maternal antibody titer, secretor status, birth method, and vaccination with the oral polio vaccine 2 days after Rotarix administration. Our findings highlight the multiple challenges faced by use of current vaccines, and identify the factors that are essential to consider in development of new rotavirus vaccines.