From early October '21, an announcement by drug company AstraZeneca (manufacturer of the Oxford COVID-19 vaccine):
AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US
Short extract (the whole thing is accessible, it's a press release, not an academic paper):
AstraZeneca has submitted a request to the US Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) for AZD7442, its long-acting antibody (LAAB) combination, for prophylaxis of symptomatic COVID-19.
[…]
In August, 2021, AstraZeneca announced high-level results from the PROVENT pre-exposure prophylaxis trial which showed AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% […] compared to placebo. Importantly, the trial population included people with co-morbidities and who may be in need of additional protection from SARS-CoV-2 infection.
[…]
AZD7442 was optimised using AstraZeneca’s proprietary YTE half-life extension technology which more than triples the durability of its action compared to conventional antibodies
As you all know, antibodies are the first line of defense against viral (and other) invaders. They disable or tag nasty stuff in the bloodstream, on mucosal membranes etc. They don't clean up the infection or work inside cells that the virus has already successfully invaded, other parts of the immune system (e.g. T-cells) do that.
High levels of relevant antibodies will blunt an infection, and reduce the risk of the immune system going crazy, which is the source of a lot of problems in severe (acute or chronic) COVID-19. They give extra time for the immune system to mount its response, hopefully quite calmly. People with co-morbidities or under-powered immune systems (e.g. elderly or immunocompromised) can really benefit from that extra help.
Antibody levels decline over time for two reasons: (1) the body stops making them as fast because the immune system doesn't invest resources in doing so without an indication that the threat continues, which is where vaccine booster shots help by telling the immune system that the (fake!) threat is still around; and (2) they naturally degrade with time, as do all complex molecules. They aren't actively cleared in the same way as many drugs, hence a single dose of monoclonal antibodies is effective for a long time, whereas antivirals like molnupravir (in another thread) need to be taken twice a day for several days (because the liver actively degrades them).
The rate of decline is characterized as a half-life (just as for radioactivity), which is the time it takes for the level to drop by half (so in twice the half life, it halves twice, i.e. it drops by a quarter). The half life of IgG (immunoglobulin G) antibodies circulating in the blood is typically about 10-21 days, but is dependent on many factors.
So what's the LAAB (long-acting antibody) bit? These cunning folk changed part of the antibody, and that change reduces the molecule's rate of dissociation (i.e. falling apart)
in vitro which reduces its rate of loss
in vivo. So that can be measured as an increase in the half-life, and that increase can be very significant. For AZD7442 AstraZeneca report a tripling (3×) of the half-life, which they say means good levels persist in the body for 9 months.
LAAB tricks are also used in other monoclonals; it's not a new thing just for COVID-19. Neat, isn't it?!
Off Topic
I wish medicines regulators had chosen a better term than EUA, which is used internationally as well as in the US. "Emergency" implies a sense of panic and corner-cutting, but the authorization process is still very strict, it just doesn't have as much data from large, long trials as full authorization because those trials have not been done. Many high-quality drugs, especially expensive drugs for rare diseases, only ever have EUA, because full trials would be difficult and uneconomic. So the term doesn't matter when intelligent adults understand it, but it allows the anti-vaxxers to imply to gullible marks that a drug or vaccine is "experimental" (well, E could be either word!) or just waved through authorization. I don't have a strong view on what the ideal term would be, but something like "Initial Use Authorization".
x5
