Notes on syphilis vaccine development

Abstract

The quest for a syphilis vaccine to provide protection from infection or disease began not long after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912. Yet, a practical and effective vaccine formulation continues to elude scientists. Over the last few years, however, efforts toward developing a syphilis vaccine have increased thanks to an improved understanding of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most likely syphilis vaccine candidates. More has been also learned about the molecular mechanisms behind pathogen persistence and immune evasion. Published vaccine formulations based on a subset of the pathogen’s OMPs have conferred only partial protection upon challenge of immunized laboratory animals, primarily rabbits. Nonetheless, those experiments have improved our approach to the choice of immunization regimens, adjuvants, and vaccine target selection, although significant knowledge gaps remain. Herein, we provide a brief overview on current technologies and approaches employed in syphilis vaccinology, and possible future directions to develop a vaccine that could be pivotal to future syphilis control and elimination initiatives.

Syphilis vaccine: challenges, controversies and opportunities

“…The ideal syphilis vaccine should provide protection against TPA infection. However, even if the vaccine is unable to completely prevent infection, it could still worth considering as a means of limiting bacteria dissemination and tissue invasiveness, blocking the establishment of latency, or preventing the disease from progressing to secondary and tertiary stages ( 113 ). Additionally, a vaccine that reduces bacterial persistence or prevents TPA transplacental invasion might also reduce the number of congenital syphilis in endemic areas, where the number of non-diagnosed infected individuals might be high, and the access to health care may be limited.…”

“…The employment of newly-developed approaches (e.g. genetic engineering), and refined bioinformatic tools enable to delve further into OMPs knowledge, benefiting future vaccine studies ( 113 , 114 ).…”

Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention

“…Although some scientists have attempted multicomponent vaccines, complete protection against infection has not yet been achieved ( 137 ). Undeniably, inducing partial protection vaccines contributes to the attenuation of transmission and, hence, blockade of progression to neurosyphilis ( 145 ). The general topic of vaccines for T. pallidum has been thoroughly addressed elsewhere and here will not go into more detail ( 136 , 146 ).…”

Insights into the protective immune response by immunization with full-length recombinant TprK protein: cellular and humoral responses

“…Indeed, since the Miller study using γ-irradiation to treat freshly isolated T. pallidum without affecting highly labile immunogenic antigens to achieve complete protection against the homologous strain of T. pallidum , the importance of antigens in T. pallidum as syphilis vaccine candidates has been highlighted 6 . Among them, the surfaced-exposed proteins have attracted attention, however, research has been greatly hampered by the incredibly slow growth of the pathogen and the paucity of surface-exposed proteins 7 , 8 . With the development of structural modeling of proteins, more information about putative surface-exposed proteins as candidate vaccinogens is being obtained 8 , 9 .…”

“…Among them, the surfaced-exposed proteins have attracted attention, however, research has been greatly hampered by the incredibly slow growth of the pathogen and the paucity of surface-exposed proteins 7 , 8 . With the development of structural modeling of proteins, more information about putative surface-exposed proteins as candidate vaccinogens is being obtained 8 , 9 . Among them, TprK may be a controversial protein not only for the location of the proteins but also for its role in syphilis vaccine 10 – 12 .…”