Credit: NIAID
Researchers on four continents have been studying the genetic diversity of M. pallidum, the bacterium that causes syphilis, in hopes of facilitating the search for a vaccine. Currently, there is no approved syphilis vaccine, and development is hampered by the bacteria’s complex nature and ability to evade the immune system.
Syphilis can cause neurological complications, adverse pregnancy outcomes, and increase susceptibility to HIV. Additionally, previous infection also does not confer long-term immunity. The number of infections is increasing in the United States and other countries. According to the Centers for Disease Control (CDC), the number of infections in the United States in 2022 will be 207,255, the highest since the 1950s. Of these, 3,755 were infants, including stillbirths.
The researchers collected and analyzed clinical and genomic data from syphilis patients in different geographic regions, including China, Colombia, Malawi, and the United States.
Whole-genome sequencing has shown that there are significant differences between the two major strains of T. pallidum, SS14 and Nichols. Although the SS14 lineage was more prevalent worldwide, the Nichols strain showed greater genetic diversity. Phylogenomics analysis showed that the Nichols strains clustered into more distinct subclades compared to the SS14 strain, indicating a more complex genetic evolution. This finding is important because different strains may respond differently to vaccines.
One key focus has been the identification of single nucleotide variants (SNVs) in outer membrane proteins that are important for vaccine development. These proteins are targets of immune responses, and their diversity can influence vaccine efficacy. In this study, we mapped SNVs to 3D protein models and discovered population-specific substitutions that may impact vaccine design and syphilis pathogenesis.
Overall, this study supports the idea that both global strain diversity and regional differences need to be considered in vaccine development to ensure widespread efficacy.
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