Many countries provide vaccines to people at high risk of monkeypox, and smallpox vaccines produced in China may be able to make a difference

The Paper's reporter Sen Ning

In less than a week, the number of confirmed monkeypox cases worldwide has soared from more than 2,000 to more than 3,000. Under the increasingly severe epidemic prevention and control situation, the health departments of the United Kingdom, Canada and other countries have successively issued new vaccination strategies. The strategy states that the third-generation smallpox vaccine MVA-BN will be provided to people who are currently at higher risk of monkeypox exposure to control the spread of the outbreak.

There are still many uncertainties about the future spread of monkeypox. Although the mainland has not yet reported any confirmed and suspected cases of monkeypox, the surging news (www.thepaper.cn) reporter learned that once the emergency occurs, the traditional Temple of Heaven strain smallpox vaccine developed and produced in China may still have the potential to play a role in preventing monkeypox.

In 1980, WHO declared that smallpox had been eradicated worldwide, and monkeypox is considered the most important positive pox virus infection in humans since smallpox eradication.

On June 22, local time, according to the statistics of the US Center for Disease Control and Prevention, the number of confirmed cases of monkeypox in the world has accumulated 3308, and the number of countries that have reported confirmed cases of monkeypox in the world has reached 42, of which 793 are confirmed cases of monkeypox in the United Kingdom, which is still the country with the largest number of confirmed monkeypox cases in the world. On 21 June, the UK Health Security Agency (UKHSA) issued new guidelines on providing vaccines to groups of men at higher risk of exposure.

In the guidelines, the UK Health Security Agency said the smallpox vaccine MVA-BN should be offered to some gay and bisexual men at higher risk of exposure to monkeypox to control the spread of monkeypox outbreaks. MVA-BN is a non-replicated attenuated smallpox vaccine produced by the Danish biological company Bavarian Nordic that is thought to be effective against monkeypox.

"While anyone can contract monkeypox, data from the latest outbreak in the UK shows that the virus spreads more across the sexual networks of lesbian, gay, bisexual and other men who have sex with men (GBMSMs)." The guidelines say. Monkeypox virus is not currently defined as a sexually transmitted infection, but it can be transmitted through body fluids, droplets, and lesions through close contact that occurs during sexual activity.

However, scholars at the University of Leicester in the United Kingdom have written in the latest issue of The Lancet that the possibility of monkeypox virus transmission through aerosols in the air cannot be ruled out.

According to the UK's Health Safety Agency guidelines, clinicians should recommend vaccinations for people who have had multiple sexual partners and who have been involved in group sex.

Mary Mary, head of immunization at the UK Health Security Agency. Dr Mary Ramsay said, "We have done extensive contact tracing efforts, which has helped limit the spread of monkeypox virus, but we continue to see an extremely high proportion of GBMSM populations in cases. By providing vaccines to high-risk populations, we hope to break the chain of transmission and thus contain the outbreak. ”

"While most cases have mild symptoms and are able to fully recover spontaneously within 3 weeks, severe illness can still occur in some people and can even lead to death, where children, pregnant women and immunosuppressed individuals are at higher risk of severe illness." Mary. Ramsey said.

"It is important at this stage that we use the available vaccines for the target population," Mary Said. Ramsey said, "In the meantime, everyone should remain vigilant for any new spots, ulcers or blisters anywhere in the body, especially if they have had close contact with their new partner." If you think you have these symptoms, avoid close contact with others and call your local sexual health center. ”

Vaccinations – the best way to control the current monkeypox outbreak

On 16 June, the European Health Emergency Preparedness and Response Agency (HERA) ordered 110,000 doses of MVA-BN smallpox vaccine from Bavarian Nordic to be supplied to EU member states, Norway and Iceland in response to the current monkeypox outbreak.

In the HEALTH SAFETy Agency's vaccination guidelines, the UK Joint Commission on Vaccination and Immunization (JCVI), which works with the UK Health Safety Agency, says vaccination is still the best way to prevent more monkeypox cases and limit the continued spread of the virus.

Currently, there is no vaccine specifically for monkeypox vaccination in the UK or Europe, but because smallpox virus and monkeypox virus belong to the same pox virus family, vaccines against smallpox are believed to provide cross-protection against monkeypox.

The third-generation smallpox vaccine, the non-replicated modified Ankara pox vaccine MVA-BN, has been approved by the UK Medicines and Health products Regulatory Agency (MHRA) and the European Medicines Agency of the European Union for use in smallpox, and the vaccine has been used in past treatment cases for monkeypox in the UK.

The UK Joint Commission on Vaccination and Immunization (JAVI) believes that vaccination should be made available to the highest-risk GBMSM individuals as soon as possible due to the large number of contacts. "Healthcare professionals are able to identify the highest-risk GBMSM individuals in populations enrolled in sexual health centers, and in the process of identification, high-risk behaviors should be labeled in a manner similar to assessing hive (HIV) pre-exposure prophylaxis (PrEP) eligibility, with risk criteria including a recent medical history of sexual partners, whether they have participated in group sex, and specific markers, such as recent (past year) bacterial steumatic transmission infections."

At the same time, priority should be given to occupational workers at high exposure risk. This includes staff providing care for monkeypox cases in high-consequence infectious disease (HCID) facilities and other medical facilities; Staff of sexual health clinics; Laboratory workers dealing with pox virus; Others who work in specialized laboratories, as well as those who work on environmental decontamination of monkeypox cases.

Considering that the MVA-BN vaccine is two doses with an interval of 28 days in between, the first dose of the vaccine should be given priority during the epidemic and a second dose should be provided to those who continue to be at risk of exposure.

For post-exposure vaccination with MVA-BN vaccine, the guidelines consider that there is evidence of very limited efficacy, but the guidelines still recommend that high-risk groups or occupational contacts should be provided with post-exposure vaccination within 4 days of their exposure to the virus; Vaccination is available for up to 14 days for people at high risk of persistent or monkeypox complications, including children aged 10 to 11 years, pregnant women, and immunosuppressed people.

However, the guidelines also state that given current epidemiological and vaccine availability, it is not recommended to implement smallpox vaccination more widely in low-risk GBMSM individuals and the general population.

The domestic Temple of Heaven strain smallpox vaccine has the potential to prevent monkeypox

Recently, the Chinese Center for Disease Control and Prevention issued the "Technical Guidelines for the Prevention and Control of Monkeypox (2022 Edition)", which pointed out that although there have been no cases of monkeypox in the mainland, people who have not been vaccinated against smallpox are generally susceptible to monkeypox virus.

On June 22, The Paper interviewed Dai Lianpan, a researcher at the Institute of Microbiology of the Chinese Academy of Sciences and the leader of the Innovative Vaccine and Immunization Research Group, on issues related to monkeypox vaccines. Dai Lianpan's team has successfully developed the world's first recombinant protein vaccine for the new crown virus. The positive pox virus is The research direction of Dai Lianpan in his doctoral period.

Dai Lianpan told the surging news (www.thepaper.cn) reporter that compared with the development of the new crown virus vaccine, the development of monkeypox vaccine has different characteristics. The new coronavirus is an RNA single-stranded virus, the genome is small, and the main protective antigen on its surface is relatively certain, while the monkeypox virus belongs to the DNA double-stranded virus, the genome is very large, and there are many types of protein antigens on the surface of the viral membrane. The current academic understanding of the protective antigen targets of monkeypox virus is not enough. Therefore, the application of technical routes such as subunit vaccines applicable to the new coronavirus to monkeypox vaccines still needs time to verify.

However, the existing smallpox vaccine to prevent smallpox virus is likely to play a better cross-prevention role in monkeypox virus. On the safety of smallpox vaccines, Dai Lianpan said that the third generation of smallpox vaccine MVA-BN, which is currently promoted in Europe and the United States, uses a genetically modified non-replicated pox vaccine Ankara strain (modified vaccinia Ankara, MVA), which has been naturally passed hundreds of times in chicken embryonic fibroblasts outside the human body, 15% of the genes have been lost, and the toxicity to the human body after vaccination is very small, and the safety factor is high. Since the vaccine is injected subcutaneously, it does not form scars on the body.

Use cases and data on the MVA-BN vaccine from Canada, the United States and other countries show that most of the reported side effects of MVA-BN are pain, redness or swelling at the injection site. Other common side effects may include fatigue, headaches, muscle soreness and aches, and nausea. These side effects are usually mild to moderate, with symptoms appearing no longer than 7 days after vaccination. No cases of myocarditis (inflammation of the myocardium) or pericarditis (inflammation of the outer layer of the heart) were found in clinical trials.

As for the efficacy of the vaccine, that is, the problem of immunogenicity, Dai Lianpan believes that although MVA-BN is two injections, the first dose can also play a certain protective role after vaccination. Previous studies by the U.S. Centers for Disease Control and Prevention have shown that single-dose MVA-BN has been observed in clinical trials to produce a powerful antibody response. In addition, data from animal studies suggest that injections of single-dose MVA-BN before and after viral attack (1 day) may provide protection for a subset of people against positive pox virus infection.

Dai Lianpan specifically mentioned that in the mainland, there is an older generation of Tiantan strain smallpox vaccine developed and produced by itself and successfully applied to the population for vaccination, although the Tiantan strain smallpox vaccine uses a replicating pox vaccine, but it has undergone 10 generations of attenuation, and the side effects are small after vaccination. In the late 1970s, after the eradication of smallpox on the mainland, the mainland population no longer vaccinated smallpox, but the Temple of Heaven strain smallpox vaccine has been produced for 40 years and as part of the national reserve. Once urgently needed, there is still potential to be effective.

According to the surging news reporter, at present, mainland medical researchers have obtained the replication defective pox vaccine virus Temple of Heaven strain, researchers through gene editing technology so that the virus lost 26 genes in the genome C to K region, thereby changing the host range, immune escape and virulence of the virus and other characteristics, so that it can not be effectively replicated in most human cells.

In another related study, domestic scholars evaluated the safety and immunogenicity of the replication-deficient Temple of Heaven strain smallpox vaccine, showing that compared with the replication type Temple of Heaven strain smallpox vaccine, the virulence of the replication defect smallpox vaccine in the brains of mice and suckling mice and rabbits was significantly reduced by more than 104 times, but at the same time, its immunogenicity also decreased accordingly, and two doses of immunity were required to achieve the effect of single immunity of the replication type Temple of Heaven strain smallpox vaccine.

However, it is understood that this non-replicated temple of heaven strain smallpox vaccine has not yet been clinically validated and put into use.

"Traditional vaccine development takes a long time to design experiments, and after repeated animal experiments and preclinical toxicological safety and efficacy verification, coupled with Phase I, Phase II, Phase III clinical trials, it often takes more than 10 years," Dai Lianpan said, "but starting from the new crown vaccine, considering the emergency situation of the epidemic and the risk-benefit ratio, many vaccines are first marketed and used, and then the subsequent impact of the vaccine is tracked and followed." This is a new change in the development of vaccines worldwide. ”

Further reading: Temple of Heaven strain smallpox vaccine

The earliest vaccine-like immunization for humans is human pox vaccination in China. According to historical records, in the sixteenth century or earlier, smallpox patients were Chinese to make a pulp of smallpox scabs and vaccinated healthy children to produce immunity to prevent smallpox. This technology has also spread around the world, protecting the lives of countless people. However, the disadvantage is that the toxicity is difficult to control, and the vaccinators still have a 2% mortality rate.

At the end of the 18th century, inspired by human pox vaccination, the British doctor Edward Jenner successfully prepared a live vaccine for the prevention and treatment of smallpox from smallpox's close relatives, less toxic cowpox, and summarized the theory. This is a model of the use of immune interventions to control high-virulent infectious diseases, and Jenner is also recognized as the father of immunology.

In 1805, the vaccinia vaccination method was introduced to China, but the strains that produced the smallpox vaccine were all from abroad. The "Temple of Heaven strain" is a Chinese vaccine made from a strain from China. According to the available data, in February 1926, a smallpox patient came to the hospital, qi Changqing, the founder and pioneer of China's biological products industry, and his assistant Li Yanmao extracted the virus from the patient, inoculated to the skin of the monkey and uploaded 2 generations, then inoculated to the skin and testicles of the rabbit for 5 generations, and then inoculated to the skin of cattle for 3 generations.

Nowadays, the "Temple of Heaven strain" has become the carrier of a variety of recombinant vaccines, such as smallpox vaccines and hepatitis B vaccines.

Editor-in-Charge: Kang Yimei

Proofreader: Ding Xiao