Comparison of Lipopolysaccharide (LPS) specific IgA and IgG avidity maturation between Vivotif Vaccinees and naturally infected enteric patients in Bangladesh

Abstract

Enteric fever, primarily caused by Salmonella enterica serovar Typhi and Paratyphi, is a potentially life-threatening systemic disease. Characterized by fever, malaise and diffused abdominal pain, it can lead to delirium, intestinal hemorrhage, bowel perforation, and even death if left untreated. High prevalence rates of enteric fever have been reported in the resource limited regions of the world, with children under 5 years of age being the largest target. Poor sensitivity and specificity of conventional diagnostic approaches result in lower or late detection of the infection. The TPTest, a novel diagnostic technique, has proved to be highly sensitive and specific for detection of the patients with enteric fever. Vaccination also is potentially important to reduce the incidence of enteric fever among young children. Vivotif, a live oral attenuated typhoid vaccine, has undergone clinical trials in different countries, including Bangladesh. However, no data on the analysis of the immune response or longevity has been carried out. The antibody avidity maturation in typhoid vaccinees or patients has also not been reported till date. Under these circumstances, this study demonstrates the lipopolysaccharide (LPS) specific immunoglobulin A (IgA) and immunoglobulin G (IgG) avidity maturation in Vivotif vaccinees and naturally infected typhoid patients aged below 5 years. Also, the age dependent variation in avidity maturation was analyzed, both in S. Typhi bacteremic and only TPTest positive patients. Vaccination with Vivotif generated IgA and IgG antibodies with significantly higher avidity that lasted throughout the study period of 28 days. Patients with S. Typhi bacteremia with an age below 5 years showed a higher IgA avidity index in the first two study day points, followed by a decrease on the second follow-up. Overall, culture positive patients had a higher IgA avidity index compared to the only TPTest positive patients, regardless of age. A similar response for IgG avidity maturation was seen among patients. Lack of significant differences in IgG avidity between different day points within a group could be attributed to the longer half-life of IgG. In short, S. Typhi bacteremic patients produced more highly avid IgA and IgG antibodies against LPS compared to only TPTest positive patients, indicating that higher bacterial load in the system may aid in generation of higher avidity antibodies.