HSV-1 vs HSV-2: what's the difference?
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Herpes simplex virus comes in two types. HSV-1 has traditionally caused oral herpes and HSV-2 genital herpes, but that line has blurred, and either type can infect either site. The distinction still matters for vaccines: a vaccine can protect against one type and not the other, as the Phase 3 Herpevac trial showed. Neither type has an approved vaccine as of 2026.
The short answer
Herpes simplex virus (HSV) — the virus behind cold sores and genital herpes — comes in two types, HSV-1 and HSV-2. For a long time the split was simple to describe: HSV-1 caused oral herpes (the cold sores and blisters in or around the mouth), and HSV-2 caused genital herpes. That line has since blurred. HSV-1 now accounts for a large share of genital herpes, and in practice either type can infect either site. [S1][S2]
How common each is
HSV-1 is one of the most common infections in people worldwide. The World Health Organization estimates that about 3.8 billion people under the age of 50 — roughly 64%, or close to two-thirds of that age group — carry HSV-1. HSV-2 is less widespread but still affects a very large number of people: an estimated 520 million people aged 15 to 49, about 13% of that age group. [S1]
(Figure note: the WHO fact sheet’s current HSV-2 estimate is 520 million, slightly higher than the “about 500 million” often quoted; the 520 million / 13% figure is used here.)
Oral vs genital — and why it is not that simple
As a general rule, HSV-1 infects the mouth and face and HSV-2 infects the genitals. But the general rule has clear exceptions. HSV-1 can be passed to the genital area — for example through oral-genital contact — and it now accounts for a substantial share of first-time (newly acquired) genital herpes, particularly among younger people and in higher-income countries. The practical takeaway is that either virus can infect either site, so the type of virus and the location of the infection are two separate questions. [S1][S2]
What is the same: lifelong latency
Whatever site they infect, both types behave the same way in one important respect: they establish lifelong latent infection — meaning the virus stays permanently in the body in a dormant, inactive state inside nerve cells and reactivates from time to time. The main difference is which clusters of nerve cells (called ganglia) each type tends to settle in: HSV-1 favors the trigeminal ganglia, the facial nerve clusters, while HSV-2 favors the sacral ganglia, the nerve clusters at the base of the spine. Both types can also be passed to others even when no sores are visible — a phenomenon known as asymptomatic shedding, in which the virus is present on skin or surfaces that look completely normal. [S2][S1]
Why the distinction matters for vaccines
Most HSV vaccine research targets HSV-2 genital disease, because it carries the larger clinical burden of recurrent, symptomatic illness. But the two types, while biologically similar, are not identical — and a vaccine can protect against one type and not the other. The clearest illustration comes from the Phase 3 Herpevac trial, an in-human study of a vaccine based on glycoprotein D from HSV-2 (a protein on the virus’s surface, abbreviated gD2). The vaccine was designed as a prophylactic vaccine — one meant to prevent infection in people who do not yet have it, as opposed to a therapeutic vaccine, which aims to treat people already infected. In the trial, the vaccine was effective against HSV-1 genital disease (58% efficacy) but showed no protective effect against HSV-2. [S3]
That result is why the statement “a herpes vaccine works” is incomplete on its own. The essential follow-up question is: works against which type? [S3]
What this does and does not mean
The two types share most of their underlying biology, and — importantly — both remain without an approved vaccine as of 2026. Keeping HSV-1 and HSV-2 distinct, much like keeping the prophylactic-versus-therapeutic distinction straight, is essential to reading herpes vaccine news accurately: a finding about one type, or one kind of vaccine, does not automatically carry over to the other. [S4][S3]