M6 live-attenuated HSV-1 strain

What M6 is

M6 is an experimental HSV-1 vaccine strain from the laboratory of Qihan Li at the Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, in Kunming, China. It is a live-attenuated vaccine: a version of the virus that has been weakened by mutating or deleting parts of genes, so that it replicates poorly but is still a whole, living virus. HSV-1 is herpes simplex virus type 1, the virus that most often causes cold sores and also causes some genital herpes. Every M6 paper on this page concerns HSV-1.

According to the 2020 PLoS Pathogens paper, the research team added mutations in three more genes, Us3, Us11 and Us12, to an earlier strain called M3. The paper’s methods describe the Us3 change being made first, in an intermediate strain, and CRISPR/Cas9 (a gene-editing tool) being used for partial deletions in Us11 and Us12. M3 already had mutations in the UL7, UL41 and LAT genes, as the group described in a 2017 paper. The result, M6, has changes in all six genes. The authors describe these genes as involved in viral gene activity (UL7), virulence (UL41), establishing latent infection (LAT; latency is the state in which HSV hides, inactive, in nerve cells) and the virus’s ability to block cell death and hide from the immune system (Us3, Us11, Us12). In cell culture, M6 formed much smaller plaques (spots of killed cells) and grew more slowly than the wild-type (naturally occurring) strain.

The authors say the idea is that a whole weakened virus presents many viral proteins to the immune system, not only the surface glycoproteins used in earlier vaccine trials. A glycoprotein is a protein with sugar chains attached; HSV uses several on its outer surface to enter cells.

Where M6 stands

All published results are from cells or animals. The papers test vaccination before exposure, so M6 is a prophylactic (preventive) design; the authors say their data show it can “prevent HSV1 disease” in mice and rhesus macaques and they do not report testing it as a treatment for people already infected.

Safety in mice. In the 2020 paper, mice infected through the nose with M6 showed no symptoms, while mice infected with wild-type virus developed illness including ulcerative eye lesions. M6 DNA levels were low in the brain, spinal cord and trigeminal ganglion (a cluster of nerve cells, called a ganglion, where HSV-1 establishes latency), but the authors report a slight increase of M6 in the nose and spleen, and tissue examination found slight infiltration of inflammatory cells in the brains of M6-inoculated mice (milder than with wild-type virus).

Immune response and challenge in mice. Mice received M6 by intramuscular injection (into muscle) and a booster dose. The paper reports that all of the boosted mice had antibodies (antibody and viral-load measurements used three mice per group), but neutralizing antibody titers (the level of antibodies that block the virus from infecting cells in a laboratory test) were low after a single dose, reaching a geometric mean of 1:4. The authors also report T-cell responses, measured as cells releasing interferon-gamma, an immune signaling protein. Thirty days after the booster, the mice were challenged with wild-type HSV-1 (strain McKrae, 10,000 plaque-forming units, through the nose). The paper reports that the M6 group had no clinical symptoms and no deaths, while its table of signs of illness lists deaths among the unvaccinated control mice. Tissue examination of the challenged, vaccinated mice found no pathological changes except slight infiltration by a few inflammatory cells. Viral DNA in the brain, spinal cord and trigeminal ganglion was lower in the M6 group.

Immune response and challenge in rhesus macaques. Rhesus macaques are monkeys used as models for human infection. They received M6 intramuscularly, with a booster two months later, and were challenged two months after that with wild-type HSV-1 (McKrae, one million CCID50, a unit of infectious virus, through the nose). The paper reports that the vaccinated animals stayed free of symptoms, while all of the unvaccinated animals developed oral blisters or redness around the eyes. Viral DNA in blood, mouth swabs and eye swabs, and in tissues including the trigeminal ganglion, was lower in the vaccinated group. Tissue examination found slight aggregation of inflammatory cells in the lungs and spinal cord of the vaccinated macaques after challenge, and inflammatory reactions in the brain and spinal cord of the controls. The authors report no viral DNA in either group at 8 months after challenge. The tables in the paper list three animals per group for the tissue analysis.

Other M6 studies. A 2022 Frontiers in Immunology paper from the same group uses M6 to study how HSV-1 infects dendritic cells, immune cells that present viral fragments to T cells. A March 2025 paper in Viruses studied M6 in macrophages, immune cells that engulf pathogens. Using a mouse macrophage cell line (RAW264.7), it reports that M6 enters mainly through the viral glycoprotein D binding a receptor like HVEM (herpesvirus entry mediator, a cell-surface protein the virus uses as a doorway); an antibody against that receptor reduced infection but did not block it completely, and that M6 produced lower levels of inflammatory signals than wild-type virus. In its mouse experiment, macrophages infected in the laboratory were injected into mice, which is not the same as vaccinating them with the virus. The paper’s results section describes the antibody and T-cell responses as similar to those from wild-type virus, and its abstract describes them as slightly lower. This paper has no challenge experiment and no protection data, so it does not show that M6 protects. It describes M6 as showing “potential as an effective vaccine immunogen”; an immunogen is a substance that triggers an immune response.

Registry and development status. A ClinicalTrials.gov search on 2026-10-26 for “attenuated HSV-1”, “M6 herpes”, “Institute of Medical Biology herpes”, “Qihan Li”, “Kunming” and related terms returned no record for M6. A few records returned by broader terms were for shingles (herpes zoster) vaccines, which are a different virus and different products. Two authors on the 2020 paper list an affiliation with Weirui Biotechnology (Kunming) Co., Ltd.; the paper states that “the authors have declared that no competing interests exist,” and its funding statement lists Chinese government science funds. The papers do not describe any license, company program, regulatory filing (such as an IND, the application to begin human trials) or planned human trial for M6, so none is stated here.

What this does and doesn’t mean for M6

These are results in mice and rhesus macaques, with HSV-1 as both the vaccine background and the challenge virus. They do not show that M6 would prevent HSV-1 infection or disease in people, and the papers contain no data in people and no safety data in people. The papers report no HSV-2 data and no genital herpes challenge; the challenges were through the nose, so they say nothing about HSV-2 or genital infection.

“Protection” in these papers means no visible symptoms and lower viral DNA in blood, swabs and tissue measured by PCR (a test that detects viral DNA) in the days after challenge. It does not mean the vaccine stopped the challenge virus from infecting the animals (sometimes called sterilizing immunity). The 2020 paper measured viral DNA in the trigeminal ganglion for months after challenge, but we found no experiment that tests for dormant (latent) virus in the ganglia by reactivating it, so whether M6 or the challenge virus can hide and reawaken is not answered by this record. Each animal group was small, and the macaque and mouse experiments used a single challenge strain given through the nose.

M6 is a replicating virus, and the 2020 paper reports low-level M6 growth in the nose and spleen of mice. The authors themselves say further studies are needed, including long-term observation of the animals and an assessment of whether M6 and the challenge virus could recombine (swap genetic material) in a living animal. The 2020 paper also notes that mice are distantly related to humans, and tested macaques as well. Neutralizing antibody titers after one dose were low in both species.

Because the 2025 paper tests infected macrophages and not vaccination, and the 2020 paper is the only one with challenge data, the evidence for protection rests on a single paper from one research group, and no independent group’s results on M6 were found.