From Kiyoshi Shiga to Present-Day Shigella Vaccines: A Historical Narrative Review

Abstract

We are at an exciting moment in time with the advancement of many vaccines, including a shigella vaccine for the world. It is instructive to look at the long road that some vaccines have traveled to recognize the remarkable accomplishments of those who were pioneers, appreciate the evolution of scientific and applied technology, and inform the future history of a vaccine that would have great potential for global health. To achieve this valuable retrospective, a narrative historical literature review was undertaken utilizing PubMed and Embase databases with relevant search terms. Retrieved articles were reviewed and information was organized into historical themes, landmark discoveries, and important vaccine development parallels. The literature reviewed was synthesized into major eras of shigella vaccine development from pathogen discovery and first attempts to empirical approaches of killed whole-cell and live-attenuated approaches, and a modern era that applied recombinant DNA engineering and structural vaccinology. The history of shigella vaccine development has largely followed the evolutionary path of vaccine development over the last 120 years, but with important lessons learned that should be considered as we embark on the future chapters of bringing to the world a safe and effective vaccine for global health.

Age-dependent acquisition of IgG antibodies to Shigella serotypes—a retrospective analysis of seroprevalence in Kenyan children with implications for infant vaccination

“…Our findings therefore support the need for the development of multivalent broad-coverage vaccines including serotypes assessed in this seroprevalence study and, additionally, that vaccination should be targeted, and ideally completed, within the first year of life in order to provide the greatest impact on the burden of shigellosis in children of endemic regions. While vaccines against multiple serotypes are being developed using various platform technologies ( 28 , 29 ), it is important that their suitability for administration very early in life (i.e., at 6 or 9 months) is tested in clinical trials.…”

Shigella Vaccines: The Continuing Unmet Challenge

“…The landscape of Shigella vaccine development is rapidly evolving, reflecting the urgency of addressing the significant global burden imposed by Shigella infections. The pursuit of a Shigella vaccine started with inactivated whole-cell S. dysenteriae formulation in the mid-20th century [60]. Over the ensuing decades, numerous vaccine strategies have been explored, from live attenuated strains to subunit vaccines.…”

Current challenges and improvements in assessing the immunogenicity of bacterial vaccines

“…Serological assays able to measure the antibody’s functionality may be critical for vaccine licensure, however, there is the need for further optimizations and standardization to overcome the key barriers to the discovery of pathogen-specific CoP. Consequently, the principal CoP for bacterial infection is still represented by the antibodies measured by ELISA and there is not a defined threshold for protection for many diseases ( Ipsen, 1946 ; Herrera et al, 2022 ). Usually, the toxin neutralization assay is employed to predict the protection against toxin-producing bacteria.…”