Regeneron’s Antibodies and Novavaxs’ Vaccine Candidate
Regeneron has come out with the first data on monoclonal antibodies against SARS-CoV-2. They report the results of administration of a combination of two antibodies targeting the spike protein, both for prophylaxis and as treatment. [1,2]
In the study, both monkeys (rhesus macaques) and guinea pigs (Syrian golden) were successfully treated and protected in a dose-dependent manner. This is confirmed both by reduced viral loads and much less severe viral pneumonia based on histopathology. The authors note that the reduction in viral load is comparable to or greater than that seen for vaccines using the same animal models.
The most effective dose regimens (50 mg/kg for prophylaxis & 150 mg/kg for treatment) are rather high doses, though in the guinea pig model the 5 mg/kg dose appears to be effective as well. The total time of prophylaxis from these antibodies is not known neither in animals nor in humans. The pharmacokinetics and pharmacodynamics of the two antibodies have not been made public, so half-life is not known.
It is notable that the treatment is comprised of two antibodies which target non-overlapping regions of the spike protein. This means that the chances of mutations which lead to the antibodies being ineffective is very low. This was monitored in the animal studies and it was noted that the antibodies did not cause the emergence of any mutations not present in the controls. Importantly, no antibody-dependent enhancement was seen.
Novavax has released their phase I (n=131. 35 day endpoint) data on their vaccine candidate. This vaccine candidate, called NVX-CoV2373, uses full-length, furin-modified, trimeric, recombinant spike glycoprotein, formulated as nanoparticles. [3,4]
The most notable part of the data is that the addition of a saponin-based adjuvant greatly boosted the antibody and T-cell response. In the most successful treatment groups (5 or 25 μg + adjuvant), patients developed levels of antibodies more than three times higher than recovered (convalescent) patients in 35 days, with two doses administered.
In terms of safety, the usual expected side-effects were seen, with some patients reporting soreness, fatigue, headaches and mild transient fever.
CD4+ T-cell responses were noted in patients dosed with protein plus adjuvant. As is expected from a phase I trial, there is no data to be seen on how long antibody and cellular responses last, nor what levels are needed for sufficient immunity.
Good news overall, hopefully both of these efforts progress swiftly and effectively.
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