Evaluating the safety and efficacy of a smallpox vaccine for preventing mpox

Researchers from Japan explore the viability and safety of LC16m8, an attenuated vaccinia virus vaccine, to prevent monkeypox

2025-05-08

(Press-News.org)

In recent years, the world has seen a surge in new and deadly infectious diseases, posing a major threat to global health. Outbreaks of COVID-19, H1N1 (swine flu), Ebola, Zika, and monkeypox are a stark reminder of our vulnerability. While some of these viruses are new and relatively unknown, others, like the monkeypox virus (mpox virus or MPXV) have been around since the 1970s but have been endemic to parts of Africa. However, the recent global outbreak of mpox—caused by a newly identified variant that is more infectious than previous strains—has raised concerns across the world, highlighting the urgent need for an effective, safe, and multivalent vaccine.

LC16m8 is an attenuated vaccinia virus strain that was originally developed in Japan for smallpox and was later approved for monkeypox in 2022. LC16m8 has demonstrated efficacy and immunogenicity in preclinical and clinical settings with non-human primates, confirming its potential against MPXV. However, further immunological and pathological analyses are required to fully characterize its properties in order to develop broadly effective mpox vaccines. To address this paucity in research, a new study evaluated the immunogenicity and safety of LC16m8 across three animal species. The study was led by Associate Professor Kouji Kobiyama, from the Division of Vaccine Science, Institute of Medical Science, The University of Tokyo, along with Professor Ken J. Ishii, also from The University of Tokyo. This study was made available online on April 15, 2025, and was published in Volume 115 of the journal eBioMedicine on May 1, 2025.

“We evaluated the immunogenicity of LC16m8 in three mouse strains and human specimens and conducted pathological analysis using a non-human primate model,” says Dr. Kobiyama. The team vaccinated three strains of mice (BALB/c, C57BL/6J, and CAST/EiJ) with LC16m8 and assessed the vaccine-induced immune responses and how well it protected the mice against mpox. Similarly, they administered a high dose of LC16m8 in cynomolgus monkeys and monitored them for safety by measuring changes in body weight, temperature, and any local or systemic reactions. Finally, they vaccinated healthy adult volunteers with LC16m8 and studied their blood samples for immune responses, including the presence of neutralizing antibodies against different MPXV strains.

Their experiments showed that LC16m8 induced strong humoral responses in all three mouse models and directly targeted MPXV antigens. This promoted germinal center B cells and follicular helper T cells that are essential for long-term immunity. Furthermore, the vaccinated CAST/EiJ mice exhibited reduced viral loads in the lung tissue, proving the vaccine’s efficacy. In the cynomolgus monkeys, the vaccine induced localized pox lesions without significantly affecting their weight, temperature, or hematological parameters, signifying the vaccine’s safety. Finally, in humans, the vaccine enhanced neutralizing antibodies against multiple MPXV variants with no serious adverse events in the follow-up period, suggesting LC16m8’s broad coverage and reinforcing its safety.

These results underscore the viability of LC16m8 as a safe, effective, and scalable choice for mpox vaccination. Furthermore, the cross-species, comprehensive analysis employed in this study provides a blueprint for developing next-generation vaccines against other poxviruses and emerging pathogens, potentially shortening response times from outbreaks to regulatory approvals to widespread public inoculation.

“Since our research validates the efficacy and safety of LC16m8, it could accelerate approval and deployment of this vaccine in regions and populations highly susceptible to mpox outbreaks, particularly in Africa. In the long run, vaccinating more people could see a significant reduction in mpox transmission rates, alleviating the pressures caused by an outbreak on healthcare systems, with the possibility of completely eliminating mpox as a public health threat,” adds Dr. Kobiyama.

Of course, further studies are still required to optimize the vaccine’s effectiveness and safety, particularly in naïve and immunocompromised populations and to explore alternative vaccine platforms. But for now, this study lays down the foundation for transforming global management strategies for mpox and other infectious diseases. “Our work can shape and guide the development of a permanent global surveillance and response system for new infectious diseases, creating more resilient societies that are better prepared for future pandemic threats,” concludes Dr. Kobiyama.

***

Reference

Authors: Kouji Kobiyama,a,b Daichi Utsumi,c Yu Kaku,d Eita Sasaki,e Fumihiko Yasui,f Tomotaka Okamura,c Taishi Onodera,e Asuka Joy Tobuse,a,l Areej Sakkour,a Ahmad Faisal Amiry,f Tomoya Hayashi,a Burcu Temizoz,a Kaiwen Liu,a Hideo Negishi,n Noriko Toyama-Sorimachi,g,o Michinori Kohara,f Tatsuya Sawasaki,h Junichi Takagi,i Kei Sato,b,d,j,k,l Yoshimasa Takahashi,e Yasuhiro Yasutomi,c and Ken J. Ishiia,b,k,l,m

Title of original paper: Immunological analysis of LC16m8 vaccine: preclinical and early clinical insights into mpox

Journal: eBioMedicine

DOI: 10.1016/j.ebiom.2025.105703

Affiliations

aDivision of Vaccine Science, The Institute of Medical Science, The University of Tokyo, Japan

bInternational Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Japan

cLaboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Japan

dDivision of Systems Virology, The Institute of Medical Science, The University of Tokyo, Japan

eResearch Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Japan

fDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Japan

gDepartment of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo

hProteo-Science Center (PROS), Ehime University, Japan

iLaboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Japan

jInternational Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Japan

kGraduate School of Medicine, The University of Tokyo, Japan

lDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Japan

mThe University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), The University of Tokyo, Japan

nInstitute for Quantitative Biosciences, The University of Tokyo, Japan

oDivision of Human Immunology, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Japan

About The Institute of Medical Science, The University of Tokyo

The Institute of Medical Science, The University of Tokyo (IMSUT), established in 1892 as the Institute of Infectious Diseases and renamed IMSUT in 1967, is a leading research institution with a rich history spanning over 127 years. It focuses on exploring biological phenomena and disease principles to develop innovative strategies for disease prevention and treatment. IMSUT fosters a collaborative, interdisciplinary research environment and is known for its work in genomic medicine, regenerative medicine, and advanced medical approaches like gene therapy and AI in healthcare. It operates core research departments and numerous specialized centers, including the Human Genome Center and the Advanced Clinical Research Center, and is recognized as Japan’s only International Joint Usage/Research Center in life sciences.

About Kouji Kobiyama from The Institute of Medical Science, The University of Tokyo

Kouji Kobiyama is an Associate Professor at the Division of Vaccine Science, Institute of Medical Science, The University of Tokyo, Japan. Prior to joining The University of Tokyo, Prof. Kobiyama was affiliated with the La Jolla Institute for Immunology (Sept 2015–April 2019), Research Institute for Health and Nutrition (2015), Research Institute for Biomedical Innovation (Apr 2010–Dec 2014), and Osaka University (Apr 2009–Mar 2010). He has received several awards for his research contributions, including the 26th Japanese Society of Biodefense Award (2014) and the NIAID Award at the Keystone Symposia on Molecular and Cellular Biology (2007).

Funding information

This research was supported by AMED under Grant Numbers JP243fa727002, JP243fa727001s0703, and JP243fa627001h0003, JP24jf0126002, JP24fk0108690, JP243fa627001h0003, and JP243fa727002, JP243fa727002, JP243fa727002 and JP243fa627007h000, and by the Research Support Project for Life Science and Drug Discovery from AMED under Grant Number JP23ama11011, and JP23ama121010, and by the Ministry of Education, Culture, Sports, Science and Technology in Japan under Grant Number 23K06577. AMED under Grant Number JP233fa827017 and JP243fa827017, JP22fk0108501.

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Evaluating the safety and efficacy of a smallpox vaccine for preventing mpox

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