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

Next Steps: The Roadmap for Sexually Transmitted Infection Vaccine Development

Vaccine development progresses through a defined set of stages, often over many years (Fig. 1). The process is expensive and thus risky for vaccine developers, but several factors can help 'de-risk' the process to facilitate vaccine development, for example, a clearly defined market for the vaccine or an advance in technology. The global STI vaccine roadmap outlines six main areas to accelerate vaccine development: first, obtaining better epidemiologic data on infection and sequelae; second, modeling the theoretical impact of STI vaccines; third, advancing basic science and translational research; fourth, defining preferred product characteristics (PPCs); fifth, facilitating clinical evaluation and vaccine introduction; and finally, encouraging investment in STI vaccine development.[20] Within each area, the roadmap delineates key action steps, many of which can be pursued in parallel to catalyze vaccine development.[20,21]

Table 1 shows selected roadmap activities that are critical for STI vaccine development, all of which help encourage investment in STI vaccines, the final action area. For example, a key activity for obtaining better epidemiologic data is research on the burden of chlamydia-associated and gonorrhea-associated PID, infertility, and ectopic pregnancy, especially in LMICs. Newer serologic tests for C. trachomatis may facilitate assessing the population attributable fraction of these outcomes due to Chlamydia.[75] The Child Health and Mortality Prevention Surveillance (CHAMPS) network, which will explore causes of neonatal deaths in developing countries, will collect much needed data on fatal neonatal syphilis and HSV infections.[76] Modeling theoretical impact is essential for all vaccines and should consider different epidemiologic and economic settings and include cost-effectiveness analyses. Existing models for HSV and chlamydia vaccines demonstrate that even vaccines with modest efficacy could have an important health impact[77,78] and could be cost-effective.[79] A 2015 WHO HSV vaccine modeling meeting stressed including HSV-associated HIV incidence and neonatal herpes as outcomes and incorporating protection against or attenuation due to HSV-1 infection in updated models. Complementary models can explore the added benefit of a gonorrhea vaccine under differing levels of antimicrobial resistance, and the potential for a vaccine to thwart such resistance.

To advance basic science, NIAID has held workshops on HSV, chlamydia, and gonorrhea vaccine development.[61,80] These workshops have brought scientists together to identify, standardize, and share reagents, immunogens, assays, and animal models to accelerate moving vaccine candidates into clinical evaluation. Important next steps include capitalizing on novel scientific advances, such as exploiting the importance of tissue-resident memory T cells in preventing HSV-2 and chlamydia infection,[46] and using novel models to evaluate vaccine candidates and conduct translational work, such as the human male urethral challenge model for gonorrhea.[81] It will be important to explore vaccine mechanisms and adjuvants used for other pathogens to find potential uses with STI vaccines, for example the OMV group B meningococcal vaccine for gonorrhea.[65]

PPCs reflect WHO guidance on desired parameters of a vaccine to meet priority public health goals, primarily for LMICs.[82] PPCs describe characteristics such as vaccine goals, target groups, immunization strategies, and data needed to ensure safety and efficacy. For example, PPCs may define whether the vaccine goal is prevention of morbidity or infection, and the minimum efficacy required to achieve a public health benefit. PPCs are now being developed for HSV vaccines. Important considerations include whether prophylactic or therapeutic vaccines are desired for LMICs, especially those with high HIV prevalence, and whether HSV vaccines should target HSV-2 only or both HSV types, which may influence the target age for immunization. Consensus building around clinical endpoints and trial design is essential for all vaccines, but may be particularly important for chlamydia vaccine. The ultimate goal is to decrease upper genital tract sequelae; however, there are challenges with measuring PID as a clinical endpoint, an insensitive, nonspecific, and multifactorial diagnosis.[13] A critical need is better measures of tubal involvement and surrogate endpoints, including biomarkers or radiologic measures of upper genital tract infection, inflammation, and damage.

Together, the roadmap activities can help generate comprehensive business cases to outline the public health rationale for each vaccine and inform decision-making, which are critical for needed investment in the field. Clearly defining disease burden and costs enables modeling of vaccine impact and cost-effectiveness and determines the vaccine market. This can be weighed against vaccine development costs, which depend on technology and the desired characteristics of the vaccine. A heightened awareness of the need for STI vaccines will also be paramount for building on current progress, as will innovative product development partnerships, which have been successful for vaccines against other neglected diseases.[83] Toward this end, an STI vaccine initiative is envisioned to bring together public health institutions, academia, donor agencies, and industry to facilitate collaboration and implement the STI vaccine roadmap.[21,84]

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