STIs: New Vaccines and Expanding Recommendations

IN RECENT YEARS, new emphasis has been placed on prevention of and treatments for sexually transmitted infections (STIs) such as gonorrhea, human papillomavirus (HPV) and hepatitis. Thankfully, research is uncovering new prevention options that may one day render these STIs a thing of the past. Here are some of the latest developments.

Preventing Gonorrhea

An estimated 82 million new cases of gonorrhea are diagnosed each year worldwide, with many of those cases occurring in low and middle-income countries (LMICs). However, the number of gonorrhea cases continues to climb in the United States as well, having increased by 118 percent since 2009, with more than 710,000 cases reported to the Centers for Disease Control and Prevention (CDC) in 2021 alone.¹

Gonorrhea is caused by the Gram-negative bacterium Neisseria gonorrhoeae. Left untreated or undertreated, it can lead to an elevated risk of human immunodeficiency virus (HIV) acquisition and transmission, pelvic inflammatory disease, infertility and neonatal health risks, as well as continued transmission of N. gonorrhoeae to sexual partners and offspring. The bacteria is highly adaptable, suppressing protective immune responses and causing repeat infections in hosts with the same strain or serotype.² Gonorrhea is also closely associated with the prevalence of other STIs, including a concurrently high incidence of chlamydial infections.

According to the World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Programme, N. gonorrhoeae has become particularly difficult to treat because it has developed a strong antimicrobial resistance (AMR). In fact, AMR has rendered many antibiotics ineffective today.

So, when WHO set a target of reducing gonorrhea incidence by 90 percent by 2030 from a 2018 global baseline,³ a challenging undertaking was ahead. No candidate vaccines for gonorrhea had been tested in humans in more than 30 years, and early vaccine development efforts had been hampered by antigenic variations. Still, the need was great and researchers heeded the call.

Today, numerous lines of vaccine research against N. gonorrheae are underway, spurred by new antigen discoveries, molecular epidemiology, mucosal immunology, availability of sequenced genomes and licensure of HPV vaccines. Some candidate vaccines focus on inducing bactericidal antibodies, and preclinical studies are looking at whether outer membrane vesicle (OMV) vaccines developed for serogroup B Neisseria meningitidis might also protect against gonorrhoea.¹ A newly licensed meningococcal OMV-based vaccine produced by GSK, Bexsero, is also offering hope as modeling suggests more than 83,000 gonorrheal infections could be prevented, including a concurrent and significant decrease in HIV infections.⁵ Most notably, in 2023, GSK received a fast track designation from the United States Food and Drug Administration (FDA) for its investigational vaccine against gonorrhea in healthy at-risk adults ages 18 to 50.²

An artificial intelligence model called Efficacy Discriminative Educated Network (EDEN) may also provide much-needed support in vaccine research since it detects antigen combinations that could decrease bacterial populations. Identifying 10 clinically relevant strains of N. gonorrhoeae, EDEN recognized two with the potential to oppose the bacteria were it to be used in a vaccine. Mouse studies confirmed that the two identified proteins did kill bacteria from multiple gonorrhea strains, and now future studies will determine whether similar results might be seen in humans.⁴

Advancing the HPV Vaccine

While Merck’s Gardasil 9 is the only HPV vaccine currently FDA-approved in the United States, in August and October 2024, respectively, WHO prequalified Yuxi Zerun Biotechnology Co’s Walrinvax two-dose schedule and an off-label single-dose administration of Xiamen Innovax Biotech Co’s Cecolin HPV vaccine. With five HPV vaccines available in the global market, WHO is moving closer to its goal of improving a sustainable supply of HPV vaccines for the prevention of cervical and other deadly cancers. A WHO position paper stated that single-dose schedules can provide comparable efficacy to a two-dose regimen,⁶ which helps to improve vaccine access, expands the number of children who can be vaccinated and reduces the burden of follow-ups to complete a vaccination series.

More than 660,000 cervical cancer cases are diagnosed globally each year, 95 percent of which are caused by HPV. Ninety percent of deaths attributed to cervical cancer occur in LMICs.⁶ With 40 different HPV strains, it is estimated that 80 percent of sexually active people will have HPV exposure at some point. In addition to cervical cancers in women, cancers of the anus, penis, vagina, vulva and throat are also caused by some high-risk strains of the HPV virus. Less lower-risk strains cause genital warts.

As mentioned, Gardasil 9 has been the only approved HPV vaccine in the United States since 2017, providing comprehensive protection of HPV high-risk strains 16 and 18 (causing 70 percent of cervical cancers, 90 percent of anal cancers and many that affect throat and genitals), strains 31, 33, 45, 52 and 58 (protection against another 20 percent of cervical cancers) and lower risk strains 6 and 11 (causing 90 percent of genital warts). The approval of Gardasil 9 superseded two earlier HPV vaccines that provided less comprehensive protection: Gardasil, which had been approved by FDA in 2006, and Cervarix, which was approved by FDA in 2009. CDC does not currently recommend those who received the Gardasil or Cervarix vaccines to receive any additional boosters with Gardasil 9 because of their protection against the most high-risk strains.⁷

The Department of Health and Human Services (HHS) Healthy People 2030 target increases to 80 percent the proportion of adolescents to receive the recommended doses of the HPV vaccine.8 Vaccination schedules are recommended for children between ages 11 and 12, although the vaccine is safe for children as young as 9. Between ages 9 and 15, the recommended dosage is two shots with the second shot six to 12 months after the first. After age 15, three shots are recommended, with the second shot one to two months after the first and the third shot six months after the first. The HPV vaccine is also safe for adults up to and including 45 years, including those who did not finish the HPV vaccine series as a child or teen or who never received the vaccine. The age limit had been 26 years until 2018 when FDA expanded the age range for some adults up to and including age 45. However, it should be noted that some insurance companies do not cover the cost of HPV vaccines past the age of 26.⁷

Those with compromised immune systems should follow the three-shot series vaccination schedule.⁷

Reporting as recent as 2023 showed more than 78 percent of girls and 75 percent of boys in the United States received at least one dose of the HPV vaccine. However, vaccination rates slightly declined from 2022, particularly among the uninsured and those covered by Medicaid. The Affordable Care Act requires public and private insurers to cover the HPV vaccine, pap tests and HPV testing for women.⁹

In May 2024, FDA expanded approvals for two self-administered swab tests that detect HPV in the cervix as part of cervical cancer screening. The self-administered tests, Onclarity HPV Assay by Becton, Dickinson and Company, and cobas HPV by Roche Molecular Systems, are options for those who wish not to receive a pelvic exam; however, the tests must be performed in a healthcare setting. An efficacy study is now investigating whether the accuracy of results from self-administered tests are comparable to sample collection by a healthcare provider during the same visit. If similar, the hope is to extend self-administered testing to be done in the home.¹⁰

Expanding Hepatitis B Vaccine Recommendations

Vaccination against Hepatitis B (HepB) is recommended for medically stable newborn infants weighing more than 2000 grams within 12 to 24 hours after birth and for children and adults up to and including age 59, including pregnant women. Depending on the vaccine brand, one or two additional shots are necessary to become fully vaccinated. In infants, doses two and three are given at 1 month and 6 months of age. Pentavalent and hexavalent vaccines that protect against five or six diseases, respectively, including HepB, may also be given for infant doses two and three.¹¹ HepB vaccines are suitable for those over age 60 if risk factors for the disease are present. Even if risk factors are absent, should patients wish to receive the vaccine, the American Association of Family Physicians states they may safely do so.¹²

FDA has approved five brands of HepB vaccines for use in the United States. Three-dose vaccine brands include Recombivax HB (Merck) and Engerix-B (GSK), both of which are approved for pediatric and adult patients, and Twinrix (GSK) for use only in adults aged 18 and older. The two-dose HepB vaccine is Heplisav-B (Dynavax), approved for adults 18 and older. It is the preferred vaccine for previously unvaccinated individuals living with HIV.¹¹ Due to limited safety data on these populations, the two-dose vaccine is not recommended for pregnant or lactating women.¹²

Combination HepB and Hepatitis A vaccines are available; however, their safety and efficacy have not been established in pediatric patients, nor have adequate studies been conducted in geriatric populations or in breastfeeding women to determine infant risk. Additionally, patients receiving injections of atidarsagene autotemcel for presymptomatic late infantile, presymptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy, Elivaldogene autotemcel for early active cerebral adrenoleukodystrophy, ocrelizumab or ublituximab-xiiy for the treatment of multiple sclerosis in adults, or teplizumab-mzwv for stages 2 and 3, type 1 diabetes mellitus should consult with their doctor before receiving a HepB injection.¹³

Once fully vaccinated, boosters are thought to be unnecessary for healthy people unless they received vaccines on an accelerated schedule, which only provides short-term protection. However, patients on hemodialysis should have annual testing of antibody levels for HepB surface antigens. When levels are too low (current AAFP recommendation is below 10mlU/mL), a booster is recommended.¹²

It is estimated that 2.4 million people in the United States are living with HepB, and more than 20,000 new infections are identified each year, yet less than one-third of U.S. adults are fully vaccinated.¹² Greater than 90 percent of babies and 50 percent of young children who do not get the HepB vaccine are at risk for lifelong infections.¹¹

To help patients understand the risks and availability of HepB vaccinations, providers should include reminders in electronic health records, patient care portal alerts and by scheduling the next in a series of vaccines when administering a previous dose. If patients are unaware of their HepB vaccination status or do not have a vaccination record, CDC recommends getting vaccinated, since there is no known risk to receiving additional HepB vaccines.

The Need for Vaccines

As of this writing, it is important to address the question of the future of vaccine research and availability for STIs. HHS and other government and nongovernmental agencies remain committed to the science of safety and logistical supply chain of these and other important lifesaving drugs.