Comb through all the risks: preclinical studies of the monkey pox vaccine will be completed by the end of the year

Preclinical studies of the monkey pox vaccine have begun at the Gamaleya Center, which are scheduled to be completed by the end of the year. Unlike the classic smallpox vaccine, which remains the only means of protection against viruses of this type, the new drug will not cause severe side effects because it does not contain a live pathogen. Scientists are currently testing two design options for the future vaccine. In February, WHO officially reported two cases of infection with a new recombinant strain of monkeypox, indicating a mutation of the virus. According to experts, the risk of a more contagious variant remains, so the development of new protective equipment remains relevant.

The world's first smallpox vaccine

Preclinical studies of the world's first specialized vaccine for the prevention of smallpox in monkeys have begun at the Gamaleya National Research Center for Epidemiology and Microbiology. Unlike existing smallpox drugs, which are still the only means of protection against infections of this type, the new development does not contain a live virus, which avoids severe side effects.

Scientists already have a candidate substance, but the final composition of the vaccine will be determined during animal experiments — they must show which combination of components will be the most effective and safe. It is planned to complete the preclinical stage by the end of the year, after which, if successful, specialists will be able to start clinical trials involving humans.

— The question is to make a modern and less reactogenic vaccine. We are conducting such a study based on recombinant technologies and will determine the composition of the drug in the near future. We do not use live, inactivated or attenuated virus. And we need to understand which antigenic composition is most effective. There are several key proteins, the use of which in the vaccine will provide protective immunity. We are looking for the best combination of them. This work should be completed by the end of the year," said Vladimir Gushchin, Head of the Epidemiology Department at the N.F. Gamaleya Center.

The monkey pox virus is considered one of the most complex: it has a large genome and a large number of proteins, as well as has an inner and outer shell. Therefore, the key task is to select the optimal protein composition for the formation of the best immune response, the specialist explained. The vaccine can be created on the basis of an adenovirus platform, similar to Sputnik V, or using mRNA technologies, like Moderna's products.

Animal studies will help determine which of the options will be the most effective. In addition, the developers will choose the optimal method of administration of the vaccine — nasal or intramuscular, and also assess the need for repeated booster administration of the drug.

The vaccine is planned to be tested on mice, rabbits and humanoid primates. During the research, scientists will evaluate the drug's ability to protect against a lethal dose of the virus, as well as its safety for the body. According to experts, the development will be aimed at a conservative part of the virus, which changes little even with mutations, while researchers continue to monitor the appearance of new variants of the pathogen.

A new strain

The monkey pox virus is endemic to Africa, but in 2022, outbreaks of infection were recorded in a number of countries, including Europe, North America and Russia. At that time, WHO recognized the emergency situation in the field of public health of international importance. The spread of the infection did not develop into a pandemic mainly because the disease is not transmitted by airborne droplets, and infection is possible only through close physical contact with the sick person or through contaminated objects. Imported cases of smallpox of monkeys are periodically recorded in Russia. The last two patients were identified on February 16 in St. Petersburg after returning from Thailand.

Like other viruses, the causative agent of monkeypox is continuously mutating. Earlier, WHO officially reported two cases of infection with a new recombinant variant of the pathogen, which combines elements of clade Ib and IIb. The patients were identified in the UK and India. Doctors stated the need to monitor the genetic variability of the infectious agent.

As reported in Rospotrebnadzor, the symptoms in both patients were typical of smallpox in monkeys. No secondary cases were identified among the contact persons. According to the Agency's estimates, risks to the general public remain low at the global level. Specialists are monitoring the situation and have the necessary means to ensure biological safety.

Nevertheless, the possibility of dangerous mutations of the virus remains. From a scientific point of view, the probability that a new recombinant will "suddenly" become both more contagious and more lethal is low, but not zero, Albert Rizvanov, head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, explained to Izvestia.

— Unlike, for example, SARS-CoV-2, smallpox viruses mutate much more slowly. Their evolution is more often associated not with point mutations, but with rearrangements and the loss or acquisition of genes that affect interaction with the immune system. For a strain to become truly pandemic-threatening, it needs a combination of several factors: high transmission through close and domestic contact, sustained transmission in populations with low levels of cross-immunity, and continued or increased virulence. There is no such data yet," the specialist noted.

The virus has the potential for further evolution, just like any pathogen. However, the scenario of a rapid global spread of the "super-dangerous" variant currently looks unlikely, Albert Rizvanov concluded.

The monkey pox virus has been known for a long time, but outbreaks outside Africa have only been reported in the last few years, which indicates its mutations. It needs to be monitored, but now the pathogen is not transmitted by airborne droplets. In any case, it is necessary to develop protection against this infection, but there is no need for mass vaccination yet, says Sergey Voznesensky, associate professor of the Department of Infectious Diseases at the Rudn University.