The clinical trials for a herpes vaccine that looked so promising in 2017 have fizzled.

Two companies have announced they are no longer actively pursuing a herpes vaccine after results from their clinical trials.

A third company in the midst of clinical trials outside the United States has become embroiled in a federal investigation.

Earlier this month, executives at Vical Incorporated the phase II clinical trial for their herpes simplex virus type 2 (HSV-2) did not meet “its primary endpoint.”

“We are extremely disappointed with the outcome and based upon these results, we will be terminating the HSV-2 program,” said Vijay Samant, president and chief executive officer for Vical, in a press release. “We are indebted to our patients for their participation and our investigators for their steadfast support.”

Samant said the biopharmaceutical company instead will be pursuing an antifungal drug that is currently in a phase II clinical trial.

Last fall, executives at Genocea they were exploring “strategic alternatives” for its herpes vaccine known as GEN-003.

A phase II trial had been completed and an eagerly awaited phase III trial had been scheduled to begin.

However, in the , Genocea officials said they were ceasing GEN-003 spending and reducing the project’s workforce by 40 percent.

Instead, the company made a “strategic shift” to the development of neoantigen cancer vaccines.

“[This] gives us the opportunity to create value for our shareholders by developing best-in-class vaccines for cancer patients and achieving leadership in this exciting field,” said Chip Clark, president and chief executive officer of Genocea, in a company press release.

In addition, Rational Vaccines’ experiments with its potential herpes vaccine is apparently in legal hot water.

Kaiser Health Arrived in April that the Food and Drug Administration (FDA) had launched an investigation into experiments in the Caribbean islands in 2016, where participants had been injected with the experimental herpes vaccine without safety oversight.

The probe is reportedly centered around the actions of William Halford, a college professor and co-founder of Rational Vaccines, who died a year ago.

In March, three people who participated in experiments overseen by Halford against Rational Vaccines over the side effects they said they suffered, according to Kaiser Health Arrived.

The developments at all three companies apparently leaves the scientific world without a major research effort for a herpes vaccine.

The need for a vaccine

Worldwide, the herpes simplex virus (HSV) affects under the age of 50.

Right now, antiviral drugs, including acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are the only treatments approved by the FDA that people can take to fight HSV.

It’s worth noting that HSV is different than the human papillomavirus (HPV).

First, the two viruses evolve differently.

Also, the herpes virus comes with a host of symptoms, including blisters, itching, and red bumps.

HPV, on the other hand, often causes no symptoms at all.

“Herpes is a very smart bug,” Dr. Jamin Brahmbhatt, a urologist with Orlando Health in Florida, told Healthline in August 2017. “With most vaccines, the way they work is they use your immune system to basically build a tolerance against, or an immunity against, whatever you’re exposed to with the vaccine… Herpes has kind of learned ways to bypass your immune system. So it’s a lot more difficult to target when it comes to vaccines.”

However, HSV and HPV also share some commonalities.

They can both be difficult to treat.

They’re also widespread, affecting millions of people in the United States and billions around the world.

But while there’s a vaccine available in the United States able to treat HPV, there isn’t one available to treat HSV.

“It’s [HSV] very prevalent, and I’d say the numbers are probably higher than the statistics would indicate,” said Brahmbhatt. “And that’s why there’s a big focus on — number one — how can we prevent someone from contracting the actual virus to avoid some of these complications? And — number two — if you’ve contracted the virus already, what can we do to control the symptoms? Because all we have right now is one class of medication that helps control the symptoms. But is there a way that we can do that better? Those are the mentalities that are going into finding some sort of vaccine.”

Editor’s note: This story was originally published on August 29, 2017 and was updated on June 19, 2018.