Future Prospects for New Vaccines Against Sexually Transmitted Infections

Sami L. Gottlieb; Christine Johnston

Disclosures

Curr Opin Infect Dis. 2017;30(1):77-86. 

In This Article

Abstract and Introduction

Abstract

Purpose of review This review provides an update on the need, development status, and important next steps for advancing development of vaccines against sexually transmitted infections (STIs), including herpes simplex virus (HSV), Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), and Treponema pallidum (syphilis).

Recent findings Global estimates suggest that more than a million STIs are acquired every day, and many new and emerging challenges to STI control highlight the critical need for development of new STI vaccines. Several therapeutic HSV-2 vaccine candidates are in Phase I/II clinical trials, and one subunit vaccine has shown sustained reductions in genital lesions and viral shedding, providing hope that an effective HSV vaccine is on the horizon. The first vaccine candidate for genital chlamydia infection has entered Phase I trials, and several more are in the pipeline. Use of novel technological approaches will likely see viable vaccine candidates for gonorrhea and syphilis in the future. The global STI vaccine roadmap outlines key activities to further advance STI vaccine development.

Summary Major progress is being made in addressing the large global unmet need for STI vaccines. With continued collaboration and support, these critically important vaccines for global sexual and reproductive health can become a reality.

Introduction

To address the profound negative impact of sexually transmitted infections (STIs) on global sexual and reproductive health, in 1989 the World Health Organization (WHO) convened an expert advisory meeting to examine prospects for developing STI vaccines.[1] The participants' assessment was rather disheartening. They noted that the only available STI vaccine at the time, against hepatitis B virus, had been only minimally implemented, and they considered the likelihood of developing a vaccine against human papillomavirus (HPV) to be very slim. Some experts felt that HPV vaccine development should not even be pursued.[1] Less than 15 years later, over half the world's infants had been immunized against hepatitis B, and the first HPV vaccines were shown to be efficacious in randomized controlled trials.[2,3] Currently, 95% of all countries include hepatitis B vaccination in their infant immunization programs, with 84% of newborns globally receiving three doses of the vaccine.[3] Because the first HPV vaccines were introduced in 2006, dramatic declines in HPV prevalence and HPV-related outcomes like genital warts have been observed in countries implementing the vaccine.[4] A new nine-valent HPV vaccine is highly efficacious in preventing HPV types causing 90% of cervical cancers,[5] a disease that still affects more than half a million women a year, primarily in low-income and middle-income countries (LMICs).[6] With financing support through Gavi, the Vaccine Alliance, HPV vaccines will soon be introduced across the hardest-hit countries, with the potential to avert millions of cervical cancer deaths.

These public health success stories provide inspiration for development of new STI vaccines. Although progress has been made over the past few decades in scaling up interventions to combat STIs, many existing and new challenges make the need for STI vaccines greater than ever.[7] For example, behavioral risk reduction efforts are cornerstones of STI prevention but have had limits in curbing STI transmission, and recent developments such as broadened use of pre-exposure prophylaxis for HIV prevention have paralleled increases in bacterial STIs in some settings.[8] STIs that have been easily treatable in the past are being threatened by new obstacles such as increasing resistance to cephalosporins for gonorrhea.[9] Lack of feasible, affordable STI diagnostic tests in many settings and the complexity and cost of screening programs have been longstanding barriers. Despite available prevention strategies, recent global estimates suggest that more than a million STIs are acquired every day.[10,11] An estimated 377 million new cases of Chlamydia trachomatis (chlamydia), Neisseria gonorrhoeae (gonorrhea), Treponema pallidum (syphilis), Trichomonas vaginalis (trichomoniasis), and herpes simplex virus type 2 (HSV-2) infections occurred in 2012.[10,11] These infections result in a number of adverse outcomes, thus effectively addressing STIs can have a range of benefits, including: improving neonatal outcomes, for example, preventing mother-to-child transmission of syphilis;[12] decreasing the burden of infertility, of which chlamydia and gonorrhea are important causes;[13,14] reducing HIV transmission, as STIs such as HSV-2 lead to increased HIV acquisition and transmission;[15] combating antimicrobial resistance, a major concern for gonorrhea;[16] and supporting the health of young people, as the genital symptoms and psychosocial consequences of STIs have important effects on quality of life.

In 2013, WHO and the National Institutes of Allergy and Infectious Diseases (NIAID) held a second technical consultation on STI vaccines, almost 25 years after the first, and found that while challenges remain, the prospects for new STI vaccines are decidedly more promising.[17] Scientific advances, in conjunction with a confluence of global efforts related to improving sexual and reproductive health and reducing vaccine-preventable diseases,[18,19] provide an opportune time to make these vaccines a reality. The latest STI vaccine consultation resulted in a global roadmap to advance STI vaccine development.[20,21] In this article, we review the need and development status for vaccines against HSV, chlamydia, gonorrhea, and syphilis, and discuss key STI vaccine roadmap activities to accelerate their advancement.

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