There are still many uncertainties in the spread of monkeypox in the future. Although my country has not yet reported any confirmed or suspected cases of monkeypox, reporters from The Paper have learned that in the event of an emergency, the traditional Tiantan strain smallpox vaccine developed and produced in China may still have the potential to prevent monkeypox.
In 1980, WHO declared that smallpox had been eradicated globally, and monkeypox is considered the most important orthopoxvirus infection in humans since the eradication of smallpox.
On June 22, local time, according to statistics from the US Centers for Disease Control and Prevention, there were 3,308 confirmed cases of monkeypox in the world. The number of confirmed cases of monkeypox in the world reached 42, including 793 confirmed cases of monkeypox in the United Kingdom. The country with the most confirmed monkeypox cases in the world. On June 21, the UK Health Safety Agency (UKHSA) issued new guidance on providing vaccines to groups of men at higher risk of exposure.
In the guidelines, the UK Health Safety Authority 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-replicating, attenuated smallpox vaccine produced by the Danish bio-company Bavarian Nordic and is believed to be effective against monkeypox.
“While anyone can contract monkeypox, data from the latest outbreak in the UK shows that the virus spreads to a higher degree within the sexual networks of gay, bisexual and other men who have sex with men (GBMSM),” the guidelines said. Monkeypox virus is not currently defined as a sexually transmitted infection, but it can spread through close contact during sexual activity, through body fluids, droplets, and diseased organisms.
However, scholars from 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 airborne aerosols cannot be ruled out.
According to the UK Health Safety Agency’s guidance, clinicians should advise people who have multiple sexual partners and who have participated in group sex to get vaccinated.
Dr Mary Ramsay, head of immunisations at HHS, said: “We have done extensive contact tracing which has helped limit the spread of monkeypox, but we continue to see cases There is an extremely high proportion of the GBMSM population in China. By providing vaccines to high-risk groups, we hope to break the chain of transmission and thus contain the outbreak.”
“While most cases are mild and spontaneously recover fully within 3 weeks, severe disease can still occur in some and even lead to death, with children, pregnant women and immunosuppressed individuals at higher risk for severe disease.” Mary Ramsay said.
“It’s important at this stage that we make available vaccines available to the target population,” said Mary Ramsay. “In the meantime, everyone should continue to be alert for any new spots, ulcers or blisters anywhere on the body, especially If they have been in close contact with a new partner. If you think you have these symptoms, avoid close contact with others and call your local sexual health center.”
Vaccination – the best way to control the current monkeypox outbreak
On June 16, the European Health Emergency Preparedness and Response Agency (HERA) ordered 110,000 doses of the MVA-BN smallpox vaccine from Bavaria Nordic for supply to EU member states, Norway and Iceland in response to the current monkeypox outbreak.
In HHS UK vaccination guidelines, the UK’s Joint Committee on Vaccinations and Immunisation (JCVI), which works with HHS UK, said vaccination remains the best way to prevent more monkeypox cases and limit the continued spread of the virus. .
Currently, there is no specific vaccine for monkeypox in the UK or Europe, but since variola virus and monkeypox virus belong to the Poxviridae family, a vaccine against smallpox is thought to provide cross-protection against monkeypox.
The third-generation smallpox vaccine, the non-replicating modified Ankara vaccinia virus MVA-BN, is approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency for smallpox, and has been used in the UK in the past Used in the treatment of monkeypox.
The UK Joint Committee on Vaccination and Immunisation believes that due to the high number of contacts, vaccination should be provided to the most at-risk individuals with GBMSM as soon as possible. “Health care providers are able to identify individuals with the highest risk of GBMSM in populations enrolled in sexual health services, and should be assessed for HIV pre-exposure prophylaxis (PrEP) eligibility during the identification process. Behavioural markers, risk criteria will include recent medical history of sexual partners, participation in group sex, and specific markers such as recent (in the past year) bacterial STIs.
At the same time, pre-exposure vaccination should also be prioritized for occupational workers at high risk of exposure. This includes staff caring for monkeypox cases in high-consequence infectious disease (HCID) facilities and other healthcare settings; staff in sexual health clinics; laboratory staff working with poxviruses; Others, and those working on environmental decontamination of monkeypox cases, etc.
Considering that the MVA-BN vaccine is two doses separated by 28 days, during an outbreak, the first dose should be prioritized and the second dose should be offered to those who continue to be at risk of exposure.
For post-exposure vaccination with MVA-BN vaccine, the guidelines believe that the evidence shows that its effect is very limited, but the guidelines still recommend that high-risk groups or occupational contacts should be provided with post-exposure vaccination within 4 days of exposure to the virus. Vaccinations; up to 14 days of vaccination may be offered for those at persistent risk or at higher risk of complications from monkeypox, including children 10-11 years of age, pregnant women, and those with immunosuppression.
However, the guidelines also state that, given the current epidemiology and vaccine availability, more widespread smallpox vaccination is not recommended for low-risk GBMSM individuals and the general population.
Homemade smallpox vaccine from Tiantan strain has potential to prevent monkeypox
Recently, the Chinese Center for Disease Control and Prevention released the “Monkeypox Prevention and Control Technical Guidelines (2022 Edition)”, which pointed out that although there have been no cases of monkeypox in my country, 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 head of the Innovative Vaccines and Immunization Research Group, on issues related to monkeypox vaccines. Dai Lianpan’s team has successfully developed the world’s first new coronavirus recombinant protein vaccine. The pox virus was the research direction of Dai Lianpan during his Ph.D.
Dai Lianpan told The Paper that compared with the development of the new coronavirus vaccine, the development of monkeypox vaccine has different characteristics. The new coronavirus is an RNA single-stranded virus with a small genome and relatively definite main protective antigens on its surface, while monkeypox virus is a DNA double-stranded virus with a large genome and many types of protein antigens on the surface of the virus membrane. At present, the academic community does not know enough about the protective antigenic targets of monkeypox virus. Therefore, the application of technical routes such as subunit vaccines suitable for 2019-nCoV to monkeypox vaccines still needs time to verify.
However, the existing smallpox vaccine against smallpox virus is likely to be able to play a better cross-prevention effect against monkeypox virus. Regarding the safety of smallpox vaccine, Dai Lianpan said that the third-generation smallpox vaccine MVA-BN currently promoted in European and American countries uses a genetically modified non-replicating vaccinia virus Ankara strain (modified vaccinia Ankara, MVA). It has been naturally passaged hundreds of times in chicken embryo fibroblasts outside the human body, and lost 15% of the genes. It can no longer be replicated in the human body. The toxicity to the human body after inoculation is very small, and the safety factor is high. Since the vaccine is administered subcutaneously, it does not cause scarring 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, headache, muscle aches and pains, and nausea. These side effects are usually mild to moderate, and symptoms do not appear more than 7 days after vaccination. No cases of myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the outer layer of the heart) have been identified in clinical trials.
As for the efficacy of the vaccine, that is, immunogenicity, Dai Lianpan believes that although MVA-BN is injected in two doses, the first dose can also play a certain protective role. Previous studies from the US Centers for Disease Control and Prevention showed that a single dose of MVA-BN produced a robust antibody response in clinical trials. In addition, data from animal studies suggest that a single dose of MVA-BN injected before and after viral challenge (1 day) may provide protection against orthopoxvirus infection in a subset of humans.
Dai Lianpan specifically mentioned that in my country, there is an older generation of Tiantan strain smallpox vaccine that was developed and produced by itself and was successfully used for population vaccination. Although the Tiantan strain smallpox vaccine uses replicating vaccinia virus, it has been attenuated for 10 generations. There are fewer side effects after vaccination. In the late 1970s, after the eradication of smallpox in my country, smallpox vaccination was no longer carried out among the Chinese population, but the Tiantan strain smallpox vaccine has been produced for 40 years as part of the national reserve. Still has the potential to be effective in the event of an urgent need.
According to surging news reporters, medical researchers in my country have obtained the Tiantan strain of replication-deficient vaccinia virus. The researchers used gene editing technology to make the virus delete 26 genes in the C to K regions of the genome, thereby changing the host of the virus. Properties such as range, immune evasion, and virulence make it ineffective for replication in most cells of human origin.
In another related study, domestic scholars evaluated the safety and immunogenicity of the replication-deficient Tiantan variola vaccine and showed that compared with the replication-deficient Tiantan variola vaccine, the replication-deficient tiantan variola vaccine was effective in mice. The virulence in the brains of and suckling mice and in the skin of rabbits is significantly reduced by more than 104 times, but at the same time, its immunogenicity is also correspondingly reduced, and two immunizations with larger doses are required to achieve the replicating Tiantan strain smallpox vaccine. The effect of a single immunization.
However, it is understood that this non-replicating Tiantan strain smallpox vaccine has not been clinically validated and put into use.
“Traditional vaccine development requires a long time for experimental design, repeated animal experiments and preclinical toxicological safety and efficacy verification, plus one phase, two, and three clinical trials, which often take 10 years. In the above time,” Dai Lianpan said, “but from the beginning of the new crown vaccine, considering the emergency situation of the epidemic and the risk-benefit ratio, many vaccines were first listed for use, and then the follow-up effects of the vaccines were tracked and followed up. This is the emergence of global vaccine research and development. new changes.”
The earliest immunization method for humans to use a similar vaccine is the human pox vaccination in China. According to historical records, in the 16th century or earlier, the Chinese made pulp from the pox scabs of smallpox patients and inoculated them into healthy children to develop immunity to prevent smallpox. This technology has also spread around the world, protecting the lives of countless people. But the disadvantage is that the toxicity is difficult to control, and the vaccinee still has a 2% mortality rate.
At the end of the 18th century, inspired by human pox vaccination, British doctor Edward Jenner prepared live vaccines from smallpox’s close relative and less toxic vaccinia for the prevention and treatment of smallpox, and made a theoretical summary. This is a model of the use of immune intervention to control severe infectious diseases, and Jenner is also recognized as the father of immunology.
In 1805, the vaccinia vaccination method was introduced to China, but all the strains used to produce the smallpox vaccine came from abroad. The “Tiantan strain” is a Chinese vaccine made with a strain from China. According to the available data, in February 1926, a smallpox patient came to the hospital. Qi Changqing, the founder and founder of China’s biological products business, and his assistant Li Yanmao extracted the virus from the patient, inoculated it into the monkey’s skin and uploaded 2 It was inoculated into the skin and testicles of rabbits for 5 generations, and it was inoculated into the skin of cattle for 3 generations. After ten generations of attenuated, a smallpox vaccinia virus with good immunity and few side effects, “Tiantan strain” “That’s how it was born.
Today, the “Tiantan strain” has become the carrier of various recombinant vaccines, such as smallpox vaccine and hepatitis B vaccine.