We have been writing about potential vaccines in late-stage trials — prophylactics in­tended to prevent Covid-19 disease and, ideally, infection with SARS-Cov-2. Another class of drugs is the therapeutics, such as the Regeneron “cocktail” the President re­ceived.

The vaccines from Pfizer / BioNTech, Johnson & Johnson / Janssen, and Moderna (et al.) are designed for active vaccination. Their ingredients kick the immune system to life and cause it to make antibodies against the SARS-CoV-2 virus, ideally durable ones that the body re­mem­bers how to make more of (when needed) for a long time to come.

The monoclonal antibody cocktails can be thought of as passive vaccination. Examples include those from Regen­eron and Eli Lilly (both companies have applied to the FDA for emergency use authorizations for their cocktails). These drugs insert directly into the body the antibodies that the immune system might otherwise generate after infection or active vaccination. Such therapeutics can be useful in people whose immune systems are not capable (for whatever reason) of mount­ing a defense against SARS-CoV-2.

(On a recent This Week in Virology podcast, TWiV #673, regular guest Dr. Daniel Griffin had a tongue-in-cheek terminology suggestion about passive vaccination. He said, in jest: “I’m thinking we should word it ‘immuni­zation’ because we have anti-vaxxers but we don’t have anyone who is anti-immunization.”)

The monoclonals take down the virus and reduce its ability to infect cells. If the person’s immune system is cap­able (not compromised), its response to infection will be blunted — there will be less virus to provoke a robust defense. Therefore the person may not develop immunity to Covid-19: once the antibody levels subside, not much lasting protection may remain. On the other hand, the patient will probably avoid the sometimes-severe second phase of the Covid-19 course, when the adaptive immune system overreacts and can end up damaging many bodily systems.

All of the monoclonals now in trials (that I know of) need to be administered intravenously. This limits their ap­plication: they could not easily be given on an outpatient basis to those early in the course of disease, or infected but asymp­tom­atic.

Antibodies, whether monoclonal or natural, do not normally last long in the human body. Dr. Griffin revealed that those from Lilly and Regeneron have a half-life in vivo of 20 to 27 days. That is, every 20+ days the antibody con­cen­tra­tion in the blood and the level of immunity drop by half. So the President’s temporary immunity is waning fast.

This brings us to the monoclonal candidate of AstraZeneca.

AstraZeneca’s monoclonals

This company (working with Oxford University) has a horse in the vaccine race, whose Phase III trial in the US has been paused since early September but is reportedly about to resume.

But AZ’s monoclonal development has not received as much attention. I for one haven’t been reading about this work until quite recently.

Over a week ago the company received $486 million from BARDA (the US Biomedical Advanced Research and De­vel­opment Authority) to conduct two Phase III trials and a manu­fac­tur­ing demonstration of its anti-SARS-CoV-2 antibody cock­tail, AZD7442. One trial will be therapeutic: it will enroll 4,000 volunteers in the US and elsewhere soon after they are hospitalized for Covid-19, to see if the cocktail improves the course of their disease. The second trial will be prophylactic: it will inject 6,000 healthy sub­jects to see if the cocktail protects them from being infected in the first place — for up to 12 months.

AstraZeneca has done something singular in developing AZD7442, after licensing its two constituent monoclonals from Vanderbilt University Medical Center last June: it has engineered the antibodies with a “proprietary half-life extension technology” to last longer in the body. They call it a long-acting antibody or LAAB. A vetted infor­ma­tional site devoted to vaccines says of AZD7442:

BARDA’s investment pays for 100,000 doses of AZD7442 if it proves safe and effective, with an option for a million more. This alone is not going to make a big dent in the pandemic even in the US, let alone worldwide; but it could be part of the solution that lets life get back to a new normal.