The 2019 coronavirus disease (COVID-19), caused by an outbreak of severe acute respiratory syndrome (SARS-CoV-2), claimed more than 5.5 million lives worldwide. Scientists have calculated that collective immunity can be achieved if 70-80% of the world's population is vaccinated. According to recent reports, to date, only 59.2% of the world's population has received at least one dose of the COVID-19 vaccine. However, in low-income countries, only 8.9% of the population received at least one dose.
The vaccination process has slowed down due to many factors, including people's doubts about the safety of vaccines, a shortage of components needed to create drugs, and a lack of resources to organize vaccination, which is typical for low-income countries. In addition, the need to store vaccines in a cold room complicated logistics and led to a delay in vaccination activities.
Since vaccination of the world's population may be delayed, scientists have realized the need to develop effective, safe, easy-to-manufacture and cost-effective prevention to prevent or reduce the risk of COVID-19 infection among the unvaccinated population.
In addition, several variants of SARS-CoV-2, such as the Delta and Omicron strains, are more contagious than the original strain and can escape the immune protection formed by the vaccine; seven of the eight approved monoclonal antibody therapies failed to neutralize the Omicron variant.
These facts point to the need for an alternative approach that would help contain the COVID-19 pandemic.
Prevention by intranasal administration of antibodies
The entrance gate for the penetration of SARS-CoV-2 into the body is the nasal mucosa, in which the level of the angiotensin converting enzyme receptor 2 (APF2) is increased – the spike protein SARS-CoV-2 binds to the host APF2. Consequently, the nasal mucosa can act as a barrier and prevent the penetration of viruses.
Antibodies against SARS-CoV-2 delivered to the surface of the epithelium of the nasal mucosa can also block viral mobility and "glue" viral particles.
In the past, prevention by intranasal administration of antibodies has proven effective against a variety of respiratory viruses and other pathogens in medicine and veterinary medicine. Based on this, the researchers hope that the presence of antibodies to SARS-CoV-2 on the nasal mucosa can effectively protect unvaccinated people and reduce the spread of the virus.
Intranasal prevention of COVID-19 with antibodies of chicken origin
A new study published on the medRxiv preprint server was devoted to the development of intranasal prevention of SARS-CoV-2.
The researchers used the receptor-binding domain of the spike protein SARS-CoV-2 as an immunogen. They immunized laying hens to obtain polyclonal antibodies against SARS-CoV-2. This method of creating antibodies is fast, inexpensive and scalable. The scientists also analyzed the effectiveness of neutralizing antibodies against currently circulating viral strains.
Phase 1 of the clinical trial showed that these antibodies are safe and well tolerated when administered to healthy people in the form of intranasal drops. The authors also studied the pharmacokinetics of immunoglobulin Y (IgY) against the receptor-binding domain of SARS-CoV-2.
They reported that IgY antibodies are concentrated in chicken eggs for 2-3 weeks after bird immunization. The level of antibodies was 50-100 mg/egg. Productivity was increased fivefold when scientists used chickens free of specific pathogens (Specific Pathogen Free, SPF).
Initially, the researchers analyzed the safety of IgY obtained from SPF chickens by intranasal administration of antibodies (4 mg/day) rats for 28 days.
This study did not reveal signs of any toxicity or innate immune response to systemic exposure to IgY.
Then IgY to the receptor-binding domain of SARS-CoV-2 was administered intranasally to healthy adult volunteers in one dose for fourteen days, and no toxic effects were detected in any of them. In addition, none of the participants after multiple doses showed the presence of IgY against SARS-CoV-2 RBD in the blood serum. This indicates the absence of systemic absorption after intranasal administration of IgY.
It is important to note that there were no signs of a systemic inflammatory immune response, the researchers did not find a noticeable increase in the level of cytokines in the blood of volunteers.
One of the advantages of IgY antibodies obtained from immunized chickens is that they carry a low risk of severe immune reactions, since they do not bind to the Fc receptor of immune cells and rheumatoid factor. This feature expands the possibility of using IgY in different categories of the population, including people with weakened immunity, the elderly and children.
However, the authors did not include people with egg yolk allergy in the study, and their reaction to the new vaccine is unknown.
Researchers believe that until collective immunity is achieved, an intranasal IgY vaccine against SARS-CoV-2 can provide passive immunization or short-term protection against COVID-19 disease. These antibodies have been shown to be effective against all circulating variants of SARS-CoV-2.
Article by L.Frumkin et al. Egg-derived anti-SARS-CoV-2 immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19: preclinical studies and randomized controlled phase 1 clinical trial published in the journal medRxiv.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru