Vaccine research is continuing to develop vaccines that give safe, effective, and long-lasting protection against coronavirus disease.
A new study published on the medRxiv platform indicates that the AZD7442 antibody cocktail provides long-lasting, effective protection against severe illness.
The spike RBD is responsible for viral binding to the human angiotensin-converting enzyme 2 (ACE2) receptor on the host cell and for viral entry into the cell to establish infection. Antibodies directed against the spike protein are capable of neutralising the virus, protecting against symptomatic infection, and restraining the course of COVID-19.
The current study examines AZD7442, a combination of two long-acting neutralizing antibodies in humans, AZD8895 (tixagevimab) and AZD1061 (cilgavimab). These were produced from convalescent COVID-19 patients’ B cells.
These compounds were created from antibodies that demonstrated high-level neutralising efficacy against the virus, as well as synergy between the two antibodies when combined. The antibodies were engineered to have a longer half-life while sacrificing effector properties such as binding to the Fc gamma receptor (FcR) and complement.
According to the study, both antibodies reacted to the viral spike protein with high affinity at different epitopes that were non-overlapping and positioned on opposite facets of the RBD. The cocktail has a 3,000-fold higher affinity for the RBD than the ACE2 receptor, and both antibodies effectively prevented RBD binding.
When tested against the virus’s currently circulating variants of concern (VOCs), both the individual antibodies and the cocktail effectively destroyed the viral particles at nanogram levels. The presence of binding at two distinct and distant epitopes meant that the VOC alterations had no effect on the drug’s neutralizing activity.
Additionally, the tweaked antibodies increased the half-life of the medication in NHPs while decreasing Fc effector functions in vitro. Antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and antibody-dependent natural killer cell activation (ADNKA) are some of these capabilities.
As a result, this drug is not related to antibody-dependent infection enhancement (ADE).
Additionally, the antibody cocktail efficiently prevented and treated SARS-CoV-2 infections in NHPs, with no detectable viral subgenomic ribonucleic acid (sgRNA) in lung fluid samples from pre-treated animals following viral challenge. The dose used was a tenth of what is used in humans (4 mg/kg vs. 300 mg).
When administered upon viral challenge, the virus was promptly eliminated from the nasal cavity and lungs within a week of illness. Thus, the cocktail protects NHPs from infection and accelerates viral clearance, all while lowering inflammatory levels in the lungs and preventing lung damage. It is expected to be beneficial in terms of infection prevention and treatment.
Neutralizing titers were much greater in animals treated with AZD7442 than in convalescent plasma. At seven days after injection, the geometric mean neutralization titers (GMT) were 22-41-fold greater whether administered intramuscularly or intravenously. Nine months after injection, levels remained thrice greater than in convalescent plasma.
The study says that a single dose of AZD7442 can protect the individual for 12 months, at least.
The researchers conclude, “AZD7442 demonstrated potent in vitro neutralization against SARS-CoV-2 VOCs, in vivo efficacy in both prevention and treatment settings of SARS-CoV-2 infection in NHPs, and extended half-life in NHPs and healthy adult participants.”
Thus, it could protect vulnerable individuals after exposure, beginning almost immediately, or enhance immunity in those who do not respond adequately to vaccination. It is also likely to help those with weakened immunity.
Moreover, its ability to speed up viral clearance and prevent serious lung damage indicates its potential use as a therapeutic in COVID-19 patients to prevent serious disease. Further trials are planned, and their results will be eagerly awaited.
A preprint version of the paper is available on the medRxiv server while the article undergoes peer review.
Photo by Alex Wong/Getty Images