▎ WuXi AppTec content team editor
Recently, a recombinant human anti-rabies virus monoclonal antibody injection for the prevention of rabies, omativir monoclonal antibody injection (English name: Ormutivimab Injection; trade name: Xunke), was approved for marketing by the State Drug Administration of China (NMPA) for passive immunization in adult rabies virus exposure.
Screenshot source: NMPA official website
Public information shows that omaltibumab injection is mainly used in combination with human rabies vaccine to supplement the antibody gap in the active immunization process of human rabies vaccine, which can directly neutralize the rabies virus in the body and play a passive immune role, which is used for passive immunity of patients who are bitten and scratched by rabies or other rabies virus susceptible animals. The approval of the drug for marketing provides a new option for passive immunity in rabies virus exposure.
What is rabies virus exposure?
Rabies virus exposure refers to being bitten, scratched, licked, or damaged skin by rabies, suspected rabies, or host animals that are uncertain of rabies, or open wounds or mucous membranes in direct contact with saliva or tissue that may contain rabies virus. In addition, rarely, rabies virus can be infected by organ transplantation or inhalation of aerosols.
According to the nature and severity of exposure, rabies virus exposure is divided into three levels.
Grade I exposure refers to a person who meets one of the following conditions:
(1) Touching or feeding animals;
(2) Intact skin is licked;
(3) Intact skin contact with secretions or excrement of rabies animals or human rabies cases.
Grade II exposure refers to a person who meets one of the following conditions:
(1) The bare skin is bitten lightly;
(2) Minor scratches or abrasions without bleeding.
Grade III exposure refers to a person who meets one of the following conditions:
(1) Bites or scratches that penetrate the skin in one or more places ("through" means that at least the dermis layer and blood vessels have been injured, and the clinical manifestation is visible to the naked eye for bleeding or subcutaneous tissue);
(2) The broken skin is licked (attention should be paid to the tiny skin damage caused by various reasons such as skin cracking and scratching);
(3) The mucous membrane is contaminated with animal saliva (such as being licked);
(4) Exposure to bats (post-exposure prophylaxis should be considered when contact between humans and bats occurs, unless the exposed person excludes bites, scratches or exposure of the mucous membranes).
Image credit: 123RF
What is passive immunity?
For rabies, there is currently no effective treatment. After exposure to the rabies virus, almost 100% of people die once they become ill. Rabies kills more than 59,000 people a year in more than 150 countries around the world, almost one person dies from rabies every 9 minutes, with 95% of cases occurring in Africa and Asia.
However, although clinical symptoms are fatal upon exposure to rabies virus, vaccines, medicines and technologies to prevent rabies deaths already exist. As long as the whole process of vaccination before the onset of the disease and the production of antibodies in the body, rabies is 100% avoidable.
At present, the prevention of rabies mainly includes active immunity and passive immunity:
Active immunity refers to the body's ability to actively produce antibodies to obtain immunity, mainly through vaccination, and the maintenance time is relatively long. Usually, it takes 1-2 weeks for rabies vaccines to induce antibodies, but antibodies can persist for several years.
Passive immunity refers to the body's passive acceptance of antibodies, sensitized lymphocytes or their products to obtain a specific immune capacity, which is characterized by a fast effect, no need to go through the incubation period, once infused immediately can obtain immunity, but the maintenance time is short.
The period after exposure to rabies virus and before vaccine-induced antibodies are produced is often referred to as the "active immune-induced protective power blank" or "high-risk infection phase." At this time, the use of passive immune agents can provide immune protection for this high-risk period, which can obtain a high concentration of neutralizing antibodies locally from the wound and block the spread of the virus in the wound. This is also the main role of the approved ommatumab injection.
The WORLD's Expert Advisory Committee on Rabies recommends that people exposed to rabies virus grade III should be thoroughly cleaned at the same time as vaccination and injected with passive immune agents infiltration around them to prevent the virus from entering the nerve tissue for rapid protection. In addition, for exposed patients with severe immunocompromised immune function, even if they are exposed to grade II.
Validity and safety are verified
Ommatidab injection contains a highly expensive anti-rabies virus monoclonal antibody NM57 (IgG1 subtype), which can specifically neutralize the linear neutralization epitope in rabies virus glycoprotein conserved antigen site I, thereby preventing rabies virus from infecting tissue cells and playing a role in preventing rabies.
In a randomized controlled Phase 3 clinical trial, the researchers evaluated the efficacy and safety of oxyltipalagmab plus human rabies vaccine in people with grade III suspected rabies virus exposure, compared with immunoglobulin (HRIG) in marketed rabies patients plus human rabies vaccine.
The results of the study showed that the post-exposure prevention of omativir monoclonal antibody combined with human rabies vaccine in people with grade III suspected rabies virus exposure reached the primary efficacy and secondary efficacy endpoints, and the safety was good, and the program setting goals were met, indicating that the experimental drug recombinant human anti-rabies virus monoclonal antibody injection was safe and effective.
All in all, the fatality rate in rabies virus exposure is close to 100%; however, the occurrence of rabies can be prevented by 100% through preventive measures such as active immunization and passive immunity.
We expect that with the arrival of ommatumab, more treatment options can be provided for rabies virus exposure to prevent the occurrence of rabies.