LC16 KMB Mpox Smallpox Vaccine Clinical Trials, Dosage, Efficacy, Side Effects
Japan-based KM Biologics LC16 KMB (LC16m8) is formulated as a freeze-dried cell culture smallpox and mpox vaccine. LC16 is a 3rd generation, live attenuated vaccine containing live vaccinia virus (LC16m8 strain) used to prevent smallpox (market authorized for all ages in 1975 in Japan / licensed under the emergency investigational new drug program. LC16m8 is currently licensed in Japan, where it was safely used by over 50,000 children in the 1970s. The WHO Strategic Advisory Group of Experts on Immunization has recommended its use. On August 2, 2022, Japan's Ministry of Health, Labour, and Welfare (MHLW) announced the approval of this smallpox vaccine for voluntary vaccinations as pre-exposure prophylaxis against the monkeypox virus. This approval followed an advisory committee review.
On November 19, 2024, the World Health Organization (WHO) Emergency Use Listed the LC16m8 vaccine. The EUL application was submitted on 23 August 2024 and accepted for evaluation on 30 August 2024. "LC16 (KMB)" (LC16m8 vaccine) is indicated for active immunization to prevent mpox disease, and the vaccine is given by multiple puncture vaccination using a bifurcated needle. It is given as a one-dose vaccine at one year of age.
The LC16m8 was an attenuated cell culture–adapted Lister vaccinia smallpox vaccine missing the B5R protein. In contrast to replication-deficient vaccines such as Modified Vaccinia Ankara, LC16m8 retains most of the vaccinia genome. Therefore, it can replicate at the inoculation site, producing a "take lesion" in vaccines. The strain LC16m8 is derived from strain Lister-Elstree by multiple passages in PRK cells at 30°C followed by additional plaque cloning. The highly attenuated strain seems to have the same potential to induce a protective immune response compared to the old type of vaccines as far as evaluated with old criteria of immunity to smallpox vaccine.
KM Biologics (SVRG Kaketsuken) is a unit of Japanese food and pharmaceuticals company Meiji Holdings, based in Kumamoto, 860-8568, Japan. Click here for the Meiji Group 2026 Vision.
LC16 KMB Mpox Vaccine Indication
LC16 KBM vaccine has been approved in Japan for smallpox and monkeypox pre-exposure prophylaxis (PrEP). A phase 3 clinical trial NCT06223919 sponsored by Universidad Nacional de Colombia launched in December 2023, Efficacy/Effectiveness, Safety, and Immunogenicity of LC16m8 Mpox Vaccine in Colombia (MPOX-COL). The study's completion date is August 2024. On August 3, 2023, the journal Human Vaccines & Immunotherapeutics published an open-label, non-randomized study investigating the safety and efficacy of smallpox vaccine LC16 as post-exposure prophylaxis for mpox. The findings of this study suggest that vaccination with LC16 is effective post-exposure prevention in individuals who had close contact with patients with mpox.
In 2017, a study concluded that 'Inoculation of LC16m8 into humans induced neutralizing antibodies against smallpox virus, and the effect was similar to that of the ACAM2000 smallpox vaccine. The results were presented at the 19th ACVVR Congress (WHO) in 2017.' Since 1976, the Japanese government has discontinued the national vaccination program for smallpox. Japan's government authorized the LC16 KMB vaccine's indication for monkeypox on August 2, 2022.
LC16 KBM Mpox Vaccine Storage
The long-term storage stability of LC16m8 (formulation: 10 years, drug substance: 5 years) confirmed the high storage stability of LC16m8.
LC16 KBM Mpox Vaccine Dosage
LC16m8 is administered as a single dose using the traditional scarification method. LC16 vaccine requires intradermal administration.
Japan Smallpox Vaccine
The Japanese government decided in 1876 that all residents should be immunized with a smallpox vaccine, and a vaccination law against smallpox started in 1910. In the twenty years from 1889 to 1908, there were 171,500 cases of smallpox, and in 1908, there were 18,139 cases. The present immunization law was implemented in 1948 under the occupation by the USA.
The Chiba Serum Institute in Japan received an unconditional license in 1975 in Japan for manufacturing the vaccines of the LC16m8 strain for the indication of "prevention of smallpox." In 1975, Chiba Serum Institute produced the vaccine in a frozen formulation, and in 1980, a lyophilized formulation was developed. The routine vaccination against smallpox in Japan halted in 1976; Chiba Serum Institute ended the vaccine production accordingly, without distributing the product in the market. The license and all product-related rights of the LC16m8 vaccine were transferred to the Chemo-Sero Therapeutic Research Institute (hereafter, "Kaketsuken") in September 2002 and after that by KM Biologics in July 2018 due to the transfer of pharmaceutical business from Kaketsuken. Manufactured vaccine lots have been maintained as part of the national stockpile. In 2002, a study was published on Japan's smallpox vaccination program.
LC16 KMB Mpox Vaccine News
November 19, 2024 - WHO Listed.
June 26, 2024 - Reuters reported authorities in the Democratic of Congo are proceeding with vaccinations.
September 15, 2022 - The Lancet published: Prevention of monkeypox with vaccines: a rapid review.
August 31, 2022 - Director of Bio Farma Honesti Basyir said Indonesia's government is targeting three monkeypox vaccines, including LC16M8 (SVRG Kaketsuken Japan).
August 5, 2022 - Australian media reported: The only other non-replicating vaccine is the LC16m8 from Japan, and scaling up production is difficult, so supplies are limited.
August 2, 2022 - Japan's MHLW presented a Plan for Monkeypox Vaccinations with KM Biologics' smallpox vaccine.
August 2, 2022 - WHO Monkeypox Research - What study designs can be used to address the remaining knowledge gaps for monkeypox vaccines?
June 14, 2022 - The Ministry of Health, Labour, and Welfare published a press release: Vaccines and immunization for monkeypox: Interim guidance.
February 3, 2021 - PLOS Pathogens published a RESEARCH ARTICLE: A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome.
April 28, 2015 - ASM Journals published: Use of the LC16m8 Smallpox Vaccine in Immunocompromised Individuals Is Still Too Risky.
March 11, 2009—The JAMA Network published Clinical and Immunological Response to Attenuated Tissue-Cultured Smallpox Vaccine LC16m8. Conclusion Administration of an attenuated tissue-cultured smallpox vaccine (LC16m8) to healthy adults was associated with high levels of vaccine take and seroconversion in those who were vaccinia-naive and yielded an effective booster response in some previously vaccinated individuals.
LC16 KMB Clinical Trials
A single-arm clinical study was conducted to evaluate the immunogenicity and safety of the smallpox vaccine for monkeypox in healthy Japanese adults (MKP-3 study). The outline of this study and its results have been published in the Clinical Research Implementation Plan and Research Outline Disclosure System (jRCT). In addition, Japan's health ministry vaccinated 50 medical workers at the National Center for Global Health and Medicine for research purposes in July 2022.
2017 - Research on the efficacy, safety, and productivity improvement of cell-cultured smallpox vaccines developed and stockpiled in Japan and on the ideal countermeasures against bioterrorism in Japan and overseas. We analyzed the ability of LC16m8 to induce neutralizing antibodies against the smallpox virus through joint research by the US CDC and this research group. Stability results of LC16m8 during long-term cryopreservation were obtained. In addition, a study on the post-exposure inoculation effect of LC16m8 was carried out.
