More anti-Omicron monoclonals and monovalent and bivalent vaccines should be developed ASAP

At this time, some countermeasures (vaccines, monoclonals and soon oral antivirals) exist for the Omicron variant rapidly outcompeting the Delta variant. Thus, I agree that the primary series vaccination and “booster” doses with the first-generation vaccines, the only ones we have currently, should be taken ASAP. As I argued in my Nov. 26 post, however, in the event Omicron-specific vaccines are needed to improve efficacy against infection and/or hospitalization, these vaccines should already be in development now. Both monovalent Omicron-specific boosters and bivalent Omicron-Delta vaccines should be ready for testing and scaled-up production if needed ASAP. Development should be done in parallel rather than in series.

The durability of protection beyond 2 months of the “booster” dose of mRNA vaccines is uncertain. Will a fourth dose be recommended in 2022? Omicron-specific second-generation vaccines could be compared with third doses of our current first-generation (2019) vaccines.

Interpreting the superb initial studies from South Africa (where I was memorably taught medicine at Baragwanath Hospital in Soweto in 1979 and 1982) should be interpreted within the context of high levels of prior infections, age distributions, and duration of time since second and third doses of vaccine. Likewise for data from Europe, Asia, the Americas and around the world.  

If these Omicron-specific vaccines are not needed, then we will be better prepared if in 2022-2023 a Pi or Rho or Omega-specific variant vaccine will be needed as either a monovalent or a bivalent vaccine, e.g., an Omicron-Pi or Omicron-Omega vaccine.

Regarding monoclonal antibodies, as of Dec. 15, sotrovimab (by GSK/Vir) was the only FDA-authorized one reported to neutralize Omicron and reduce hospitalization rates in outpatients. Sotrovimab binds to a region of the virus that is not part of the receptor-binding domain and thus is not inhibited by the multiple mutations in Omicron’s receptor-binding domain.

This morning, however, AstraZeneca stated in a press release that their new combination monoclonal antibody (Evusheld), having received an emergency use authorization from FDA last week as the first and only monoclonal for COVID pre-exposure prophylaxis, appears effective in vitro against Omicron (but note the difference in neutralizing potency compared with the 2019 virus):

“In this study, Evusheld’s Inhibitory Concentration 50 (IC50), a measure of neutralising potency of an antibody, was 171 ng/ml and 277 ng/ml in two confirmatory tests, which is within the range of neutralising titres found in someone who has been previously infected with COVID-19. Evusheld’s IC50 for the original strain of SARS-CoV-2, previously referred to as the Wuhan strain, was approximately 1.3 ng/ml and 1.5 ng/ml, respectively.”

“The early data [was] generated by pseudovirus testing of the full Omicron variant spike against the combination of tixagevimab with cilgavimab, the antibodies that comprise Evusheld … The study was performed independently by investigators at the US Food and Drug Administration (FDA), Center for Biologics Evaluation and Research.”

More long-lasting monoclonals (~ 6 months), for Omicron and beyond, should be developed ASAP.

Lastly, although no oral antiviral drugs are available today, a potential breakthrough is imminent. FDA can be anticipated to decide in the coming weeks whether to grant an emergency use authorization to Merck’s molnupiravir and/or Pfizer’s Paxlovid, near the coming Omicron peak surge.