New Super Monoclonal Antibody Treatment Against Omicron Strains BA.1, BA.2 + All Variants
There was a recent study released on a new monoclonal antibody named 87G7 which proved to be highly protective pre exposure, and post exposure against all SARS-CoV-2 variants + strains including Omicron BA.1 & BA.2. As there are currently few effective antibody treatments against Omicron BA.1 and BA.2, this could be an answer to the deficit. That said, this publication will be broken down into 2 parts:
Explanation of data from the new monoclonal antibody study
What this new potential treatment means for individuals seeking preventative, and post exposure care for COVID-19
The study
This study aimed to identify an effective neutralizing monoclonal antibody against the Omicron variant as many are now ineffective against it. Specifically, Sotrovimab and Bebtelovimab (Eli Lilly’s new offering) seem to still efficiently neutralize Omicron, but remain in short supply.
To begin, humanized Harbour H2L2 mice were immunized with SARS-CoV-2 spike protein, specifically with a purified trimeric (3 region/protein) S ectodomain (outer part) from the ancestral strain. As a result, those mice generated an effective monoclonal antibody named 87G7 against the spike protein of multiple SARS-CoV-2 variants, and strains. Specifically against the spike Ace2-RBD (receptor binding domain) of Omicron BA.1, and BA.2.
Then those mABs (87G7) from hybridoma supernatants aka monoclonal antibodies generated by mice after exposure to SARS-CoV-2 spike proteins, were tested for potency against engineered pseudoviruses (special lab created Calu-3 cells, made to look like Alpha, Beta, Gamma, Delta, & Omicron) with S E484K mutation. In other words, the monoclonal antibodies were tested against pseudoviruses resembling different strains of SARS-CoV-2 like Alpha, Beta, Gamma, Delta, + Omicron, and also live virus strains (SEE FIG. 1 📸). Moreover, mAB’s 87G7 were compared to Regeneron monoclonal antibodies 10933 & 10987 for effect (SEE FIG. 1 📸).
FIG 1: Overall, high IC50 levels for Regeneron 10933 & 10987 were seen against Omicron in 1.) pseudovirus, and 2.) live virus, 1229 (BA.1), >6000 (BA.1), >1000 (BA.1) and >1000 (BA.2) respectively. Compared to low IC50 levels for 87G7 against Omicron in 1.) pseudovirus and 2.) live virus, 2.4 (BA.1), 6.7 (BA.1), 10.2 (BA.2) respectively. The lower the IC50 numbers, the more effective the antibody was against Omicron. That said, IC50 was lowest for the monoclonal antibody 87G7 against Omicron compared to Regeneron that demonstrated a 350-fold loss in IC50 (SEE RED BOX E BELOW).
FIG. 1 📸
Next, that same monoclonal 87G7 created by humanized mice was tested in other similar humanized mice who were nasally challenged with SARS-CoV-2 variants D614G, Alpha, Gamma, & Delta. Essentially, the new monoclonal antibody (87G7), or control isotypes (aka control group) were injected into different groups of mice either 16 hours before (prophylactically -as a preventative) or 1 day after (as a treatment against COVID-19) being exposed to different variants. Importantly, mice were scored for weight loss, and 5 days after after viral challenge lung samples were collected. The result, mice treated with 87G7 before viral challenge experienced a decrease in live virus within lung tissue by 1-3 orders of magnitude compared to isoptype treated mice (FIG. 2📸, C). Also, 87G7 delivered before & 24 hours after viral challenge resulted in less weight loss compared to isotype treated mice (FIG. 2📸, A,D). Furthermore, 87G7 given 24 hours after viral exposure reduced lung antigen levels & and infectious SARS-CoV-2 lung titers by 2 orders of magnitude against wild type variant (FIG. 2📸, D-F). In other words, the monoclonal antibody was very effective against D614G, Alpha, Gamma, and Delta variants (FYI-Omicron is tested in the next group).
FIG. 2 📸
Next, a similar scenario was played out in hamsters. However, this time monoclonal effectiveness against Omicron BA.1 was tested in addition to all other variants previously listed. To recap, groups of hamsters were injected with either monoclonal 87G7 (treatment), or isotype (control) 24 hours before or after 12 hours after being intranasally challenged with SARS-CoV-2 variants. 4 days after, infectious lung samples were collected then measured. The results, hamsters given the monoclonal 87G7 exhibited infectious virus titers at almost undetectable levels compared to isotype group (FIG. 3 A 📸). Also, if you look at FIG. 3 📸 below, you see that the administration of novel monoclonal antibody (87G7 compared to isotype) resulted in less lesions, and lower semi quantitative antigen scores against all variants of concern + Omicron BA.1 FIG. 3 📸 B,C). Finally, therapeutic treatment with 87G7 24 hours after viral exposure exhibited a greater than 3 log reduction infectious viral lung titers (FIG. 3, D-F 📸). This is all because of the ACE2-RBD blocking effect that 87G7 exhibits against most variants, especially Omicron.
FIG. 3 📸
So what does this mean for individuals seeking preventative, and post exposure care for COVID-19
To set the table and to be clear, because SARS-CoV-2 mutated into Omicron, older engineered treatments are no longer as efficacious against the novel strain. That means treatments like vaccines, certain antivirals, and monoclonal antibodies don’t protect as well. However, this new monoclonal antibody could be a saving grace for healthcare workers, those at high risk, and the general population.
It is important to note that the only somewhat protective monoclonals against Omicron BA.1, and BA.2 are Sotrovimab, and Bebtelovimab. Regrettably, most people cannot access the aforementioned as they are being closely regulated by the government and are in short supply.
Next, current vaccines target the original wild-type variant, and protection wanes over time. As a testament to that, new Israeli data is showing that even a 4th dose is only providing a mild transient effect. To be specific, a 4th dose from Pfizer revealed vaccine efficacy against Omicron to be 31%, and Moderna 11%.
As far as FDA EUA approved antiviral pills like Paxlovid, they are nearly impossible to get ahold of. The government is regulating currently circulating doses which is creating a barrier for deserving patients. Furthermore, antivirals need to be taken at the onset of disease. Unfortunately, by the time patients are granted access to them, they are sometimes 7-10 days in- again, government regs are to thank for that. For those reasons, antivirals have not been as effective as they could be.
As a side note, Fluvoxamine, a cheap antidepressant drug is being used to combat COVID. However, many physicians are not privy to the new data on this. The sad part is, Fluvoxamine has been an FDA approved drug for years and physicians could prescribe it off-label. Regardless, many doctors choose not to as the treatment is so novel.
Let’s fast forward to 2/17/22. A new monoclonal antibody study was released on a preprint server where it demonstrated excellent efficacy against Omicron BA.1, and BA.2 strains. Yes, that is the one being explained in this publication. So naturally, one of the very next steps would be a randomized controlled trial in humans. Considering the lack of effective treatments, this should be a priority.
You see, if this drug did good in human clinical trials, it could provide an effective prophylactic, and post exposure COVID treatment for many. For instance, healthcare workers, and those at highest risk- immunocompromised, elderly, etc. Of course, enough doses would have to be manufactured and distributed and the government would need to loosen their current prescribing restrictions on physicians and pharmacies. As you can see, there are many factors at play.
Additionally, it is likely this monoclonal would be provided in urgent care and primary care settings which would reduce the burden on hospitals. That is good because an influx of Omicron patients seeking monoclonal treatments would saturate the census, thus reducing the quality of care delivered to all hospital patients, thus increasing medical errors.
All and all, the world is in dire need of diverse types of COVID-19 treatments amidst a variant that has substantially reduced the effectiveness of ones widely available. Maybe, this new monoclonal antibody 87G7 could be the answer. How do you feel about it?
LETS CONNECT:
I pray for wisdom and brilliance in all those seeking scientific truth. I am hopeful 87G7 will be an answer to our prayers. But, I am not holding my breath. I will research this just as I researched vaccines; we will see.