Moderna’s two-pronged approach to combating emerging SARS-CoV-2 variants
Moderna is taking a two-pronged approach to addressing potentially weakened vaccine protection against SARS-CoV-2 variants by evaluating an additional booster shot of its current vaccine — a solution that could apply to multiple mutants — and a new booster candidate designed against a specific variant.
In a tweet, Acting FDA Commissioner Janet Woodcock said the agency is considering regulatory pathways for authorized COVID-19 vaccines or other products that would require changes in response to emerging variants, but hasn’t announced specific plans. FDA has longstanding experience with mutating viruses through its oversight of flu vaccines, which are updated on an annual basis.
Moderna Inc. (NASDAQ:MRNA) gained $15.96 (12%) to $147 Monday when it announced plans to test a second booster shot of Moderna COVID-19 Vaccine (mRNA-1273). On a conference call Monday, CMO Tal Zaks said third injection would likely be given 6-12 months after the initial two in the vaccination schedule, but not sooner.
The company also plans to advance mRNA-1273.351, designed as a booster against the B.1.351 (501Y.V2) variant first identified in South Africa, into preclinical and Phase I testing; its development timeline is not disclosed.
The biotech also published Monday, with NIH’s National Institute of Allergy and Infectious Diseases, a bioRxiv paper showing antibodies evoked by Moderna COVID-19 Vaccine were less potent against pseudoviruses with spikes bearing all the B.1.351 mutations vs. the D614G mutation alone.
Neutralizing geometric mean titers (GMTs) in sera from eight Phase I volunteers fell 6.4-fold (p=0.0078) against the variant’s spike, but remained above thresholds that protected non-human primates in SARS-CoV-2 challenge titers.
On Monday’s call, Moderna President Stephen Hoge pointed out that all eight trial participants' sera remained "able to completely neutralize" the pseudovirus variant, suggesting Moderna COVID-19 Vaccine will remain effective against B.1.351.
The participants’ titers were also 2.7 times lower in assays using spikes that had only D614G plus the three receptor-binding domain (RBD) mutations, which are also present in the P.1 variant — also known as 501Y.V3 —first identified in Brazil.
There was no drop in neutralizing GMTs in assays incorporating mutations from other variants, including the B.1.1.7 variant, also called 501Y.V1, that was first seen in the U.K.
BioNTech SE (NASDAQ:BNTX) and Pfizer Inc. (NYSE:PFE) similarly reported last week in bioRxiv that sera from individuals vaccinated with Comirnaty (BNT162b2) were equally able to neutralize pseudoviruses with B.1.1.7’s spike and the spike from the reference strain isolated in Wuhan.
BioNTech has said that if a SARS-CoV-2 variant develops that renders Comirnaty insufficiently protective, it could create a modified vaccine within about six weeks.
Monday’s paper adds to several others published in bioRxiv last week suggesting minimal loss of protection against the variants by the first tranche of vaccines.
An outstanding question is whether CD8+ T cell-mediated immunity, which will likely be less vulnerable to mutation-mediated protein structure changes, will exhibit similar minimal loss of protection against SARS-CoV-2 mutations.
On Tuesday, Gritstone Oncology Inc. (NASDAQ:GRTS) unveiled a mixed-modality vaccine regimen — chimpanzee adenoviral vector antigen delivery for prime vaccination and self-amplifying RNA delivery for the boost — slated to begin Phase I testing this half with support from NIAID. Both vaccine candidates will target the spike; the second vaccine candidate will also deliver non-spike CD8+ T cell epitopes.