Complex adaptive immunity to enteric fevers in humans: lessons learned and the path forward.

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Typhoid and paratyphoid fevers, caused by Salmonella Typhi and Salmonella Paratyphi, are significant global health issues.
• Current vaccines offer limited protection, highlighting the need for improved typhoid and paratyphoid vaccines.
• A key challenge in developing better vaccines is the absence of defined immunological correlates of protection.

Purpose of the Study:

• To critically evaluate current knowledge on cell-mediated immunity (CMI) and humoral immunity against Salmonella Typhi and Salmonella Paratyphi in humans.
• To explore recent advancements in understanding host-pathogen interactions, including gut microbiota influence and immune cell homing.
• To identify gaps in understanding immune responses crucial for effective vaccine development.

Main Methods:

• Review of existing literature on human immune responses to Salmonella Typhi and Salmonella Paratyphi infections and vaccinations.
• Analysis of studies measuring systemic and local immune responses, including antibody production, B-cell memory, T-cell proliferation, cytokine profiles, and cytotoxic T-lymphocyte activity.
• Assessment of research on the interplay between gut microbiota and immune responses to attenuated Salmonella Typhi strains.

Main Results:

• While S. Typhi-specific antibodies and memory B cells are induced, their protective role remains unclear.
• Cell-mediated immunity, including lymphoproliferation, multifunctional cytokine production, and CD8+ T-cell responses, is likely critical for protection.
• Local gut immunity and the homing of immune cells to the gut are important considerations for enteric fever protection.

Conclusions:

• A comprehensive understanding of both CMI and humoral immunity is essential for developing effective typhoid and paratyphoid vaccines.
• Further research is needed to define correlates of protection and optimize vaccine strategies targeting enteric fever pathogens.
• Investigating the role of the gut microbiota and immune cell trafficking may reveal novel approaches for vaccine design.