Moderna Announces Positive Initial Booster Data Against SARS-CoV-2 Variants of Concern

Moderna ^ | May 5, 2021 | Moderna

[Cathi]

Participants in Phase 2 study were tested for pseudovirus neutralization (PsVN) titers prior to boosting approximately 6 to 8 months after their primary vaccination series. Although titers versus the wild-type SARS-CoV-2 virus remained high, with 37 of 40 participants having detectable titers, titers against the variants of concern (B.1.351 and P.1) were much lower, with approximately half of participants having titers below the assay limit of quantification prior to boosting. Two weeks after receiving either mRNA-1273 or mRNA-1273.351, PsVN titers were boosted in all participants and all variants tested. Following boost, geometric mean titers (GMT) against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination1.

mRNA-1273.351 appeared more effective at increasing neutralization titers against the B.1.351 variant when compared to mRNA-1273, as evidenced by higher mean GMT levels already at 15 days following booster dose (GMT = 1400 for mRNA-1273.351; GMT = 864 for mRNA-1273). The relative decrease in neutralizing titers between the wild-type (D614G) and B.1.351 assays also improved with mRNA-1273.351 booster, from a 7.7-fold difference prior to boost to a 2.6-fold difference 15 days after boost, suggesting a potentially more balanced immune response against the tested variants.

Safety and tolerability profiles following third dose booster injections of 50 µg of mRNA-1273 or mRNA-1273.351 were generally comparable to those observed after the second dose of mRNA-1273 in the previously reported Phase 2 and Phase 3 studies. A review of solicited adverse events indicated that the vaccine boosters were generally well tolerated. The majority of adverse events were mild or moderate in severity. The frequency of any Grade 3 solicited local or systemic adverse events was 15% after the third dose of mRNA-1273 and 10.5% after the third dose of mRNA-1273.351.

[WildHighlander57]

From the article:

“...Besides injection site [muscle] and lymph nodes [proximal and distal], increased mRNA concentrations (compared to plasma levels) were found in the spleen and eye.
...
Low levels of mRNA could be detected in all examined tissues except the kidney.
...
The mRNA constructs were not measurable after maximum 3 days in tissues other than the muscle, lymph nodes, and spleen.
...”

Looks like it stays 1-3 days mostly in

Muscle where injected
Lymph nodes
Spleen
Eye
Kidney

Hmm, what about this:

“...No dedicated studies on absorption, metabolism, and excretion for mRNA-1273 have been submitted. This is generally acceptable with regards to the nature of the vaccine product. ...”

[WildHighlander57]

Many thanks for this information!

[Cathi]

It is generally thought that the sole function of viral membrane fusion proteins is to allow the viruses to bind to the host cells for the purpose of viral entry into the cells, so that the genetic materials can be released and the viral replication and amplification can take place. However, recent observations suggest that the SARS-CoV-2 spike protein can by itself trigger cell signaling that can lead to various biological processes. It is reasonable to assume that such events, in some cases, result in the pathogenesis of certain diseases.