EXECUTIVE SUMMARY

The National Institute of Allergy and Infectious Diseases plans to commit $41.6 million over five years to support four clinical research centers to develop vaccine candidates for syphilis, gonorrhea, and chlamydia.

• Researchers at the University of Connecticut School of Medicine will spearhead efforts to develop a syphilis vaccine candidate. Syphilis is the second-leading cause of miscarriage and stillbirth worldwide.

• The Gonorrhea Vaccine Cooperative Research Center will be located at the Uniformed Services University of Health Sciences in Bethesda, MD. A second gonorrhea vaccine center will be established at Georgia State University.

• The University of North Carolina at Chapel Hill will serve as the center for chlamydia vaccine research


With more than 1 million new sexually transmitted infection (STI) cases diagnosed each day on a global basis, public health officials are calling for new approaches on the scientific front to combat the rising number of infections.1

Leaders from the National Institute of Allergy and Infectious Diseases (NIAID) called for a “refocused, dedicated, and intensive biomedical research program” in a recent perspective piece. NIAID Director Anthony Fauci, MD, Robert Eisinger, PhD, special assistant for scientific projects in NIAID’s Immediate Office of the Director, and Emily Erbelding, MD, director of the agency’s Division of Microbiology and Infectious Diseases, co-authored the paper.

Response to Significant Need

The agency plans to commit $41.6 million over five years to support four clinical research centers in an effort to stimulate collaborative, multidisciplinary research on the bacteria that cause syphilis, gonorrhea, and chlamydia. The hope is for each center to identify at least one candidate vaccine ready for testing in clinical trials by the end of the five years.

“At this time, no vaccines are available to prevent syphilis, gonorrhea, or chlamydia,” said Fauci in a statement. “However, research at these new centers should help fill the pipeline with several vaccine candidates that have feasible pathways to licensure in the U.S.”2

Researchers at the University of Connecticut School of Medicine will spearhead efforts to develop a syphilis vaccine candidate. Led by Justin Radolf, MD, professor at the University of Connecticut School of Medicine, and Michael Anthony Moody, MD, associate professor at Duke University, the center will receive up to $11 million over five years to study potential candidates.

The need for a vaccine is significant. Syphilis is the second-leading cause of miscarriage and stillbirth worldwide.3 According to the CDC, there were 30,644 cases of early syphilis in the United States in 2017, representing an increase of 76% since 2013.4

“An effective syphilis vaccine would represent a triumph for biomedical research over an ailment that has defied conventional public health strategies for prevention and control,” said Radolf. “If successful, the scientific and public health impact of our approach will extend well beyond syphilis and establish a model to tackle other pathogens.”5

Using structural biology approaches, scientists plan to investigate surface-exposed proteins within the outer membrane of Treponema pallidum, the bacterium that causes syphilis, in the search for vaccine targets.

Two of the NIAID-funded centers will aim their efforts at gonorrhea, which is caused by Neisseria gonorrhoeae. CDC statistics indicate that more than a half-million gonorrhea diagnoses were reported in 2017, representing a 67% jump from 2013.4 Impetus to develop an effective vaccine candidate stems from the fact that the bacteria that cause gonorrhea have become resistant to most antibiotics.6

Nine Candidates Identified

Scientists recently completed proteomic profiling on all the proteins produced by 15 gonorrhea strains; among the isolates were World Health Organization-maintained reference strains that show all known profiles of gonococcal antimicrobial resistance.7 Nine new potential vaccine candidates were identified as a result of the research.

The NIAID-funded Gonorrhea Vaccine Cooperative Research Center will be led by Ann Jerse, PhD, of the Uniformed Services University of Health Sciences in Bethesda, MD. Reseachers from Emory University, University of North Carolina, Duke University, University of New Mexico, Oregon State, and the University of Virginia will participate in the center’s efforts, which will receive up to $10.7 million over five years.

Cynthia Cornelissen, PhD, director of the Center for Translational Immunology in the Institute for Biomedical Sciences at Georgia State University, will head efforts in the second of the NIAID-funded centers.7

What About Chlamydia?

Chlamydia is the most commonly reported STI in the United States. According to the CDC, more than 1.7 million cases were diagnosed in 2017, with 45% among females ages 15-24.4

Efforts to develop an effective chlamydia vaccine will be based at the University of North Carolina (UNC) at Chapel Hill. Leading the center efforts is Toni Darville, MD, chief of the UNC Division of Pediatric Infectious Diseases, vice chair of pediatric research and a distinguished professor of pediatrics, microbiology, and immunology at the UNC School of Medicine. Up to $10.7 million over five years will be issued by NIAID to advance science on chlamydia vaccine research.

Previous research funding was awarded to Darville and scientists at the University of Pittsburgh to study the T-cell response against chlamydia.8 Since chlamydia multiplies inside host cells in a protective vacuole, researchers are looking for a robust T-cell response for protection.

In the first of three projects funded through the UNC center, Darville and researchers at the University of Pittsburgh will further study candidate vaccine antigens identified in their previous project. With the University of Pittsburgh as the clinical core, scientists will enroll 150 women at high risk of chlamydia infection into a longitudinal study. All women will be tested for chlamydia, treated with an antibiotic to clear infection, and followed over the next year to check for reinfection. Samples will be sent to UNC for further T-cell antigen testing, while collaborators at the German Cancer Research Center in Heidelberg will examine the women’s antibody responses.

REFERENCES

  1. Eisinger RW, Erbelding E, Fauci AS. Refocusing research on sexually transmitted infections. J Infect Dis 2019;doi:10.1093/infdis/jiz442.
  2. National Institute of Allergy and Infectious Diseases. NIH awards will advance development of vaccines for sexually transmitted infections. May 9, 2019. Available at: https://bit.ly/2M8owhW.
  3. Korenromp EL, Rowley J, Alonso M, et al. Global burden of maternal and congenital syphilis and associated adverse birth outcomes — Estimates for 2016 and progress since 2012. PLoS One 2019;doi:10.1371/journal.pone.0211720.
  4. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2017. Oct. 15, 2018. Available at: https://bit.ly/2pIeV8y.
  5. Connecticut Children’s Medical Center. Connecticut Children’s co-develops first syphilis vaccine. May 20, 2019. Available at: https://bit.ly/35sVa5t.
  6. Kirkcaldy RD, Ballard RC, Dowell D. Gonococcal resistance: Are cephalosporins next? Curr Infect Dis Rep 2011;13:196-204.
  7. Noinaj N, Buchanan SK, Cornelissen CN. The transferrin-iron import system from pathogenic Neisseria species. Mol Microbiol 2012;86:246-257.
  8. Russell AN, Zheng X, O’Connell CM, et al. Analysis of factors driving incident and ascending infection and the role of serum antibody in Chlamydia trachomatis genital tract infection. J Infect Dis 2016;213:523-531.