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Moderna's COVID-19 vaccine may work better in the elderly than competitors’

Immunogenicity from Moderna’s COVID-19 vaccine sustained in older adults

Moderna’s Phase I COVID-19 vaccine readout shows induction of antibody, T cell responses in elderly volunteers as robust as in younger adults, suggesting similar protection in the more vulnerable group.

Aug 27, 2020 | 2:05 AM GMT

New Phase I data suggest Moderna’s COVID-19 vaccine maintains its immunogenicity in elderly individuals better than two other leading vaccines. Assuming neutralizing antibodies are key determinants of protection, and that the early results hold up, that could mean mRNA-1273 will do a better job of protecting the high-risk population.

The weakening immune systems in older individuals have been a concern for vaccine developers, given that immune function is needed for vaccines induce protection against pathogens. 

During a Wednesday meeting of the Advisory Committee on Immunization Practices (ACIP), Moderna Inc. (NASDAQ:MRNA) presented encouraging immunogenicity data from two older cohorts in the company’s Phase I trial and said the subjects’ adverse events were mostly mild to moderate, with the most severe being grade 3 fatigue.

On a separate conference call Wednesday to discuss the data, CMO Tal Zaks said neutralizing antibody titers induced by 100 µg mRNA-1273 — the dose Moderna is testing in Phase III — were “generally the same” across the study’s three age groups: 18-55, 56-70 and 71 and older.

The 71 and older group in Moderna’s study had titers that were just a hair less than those in the 18-55 group, and about 25% less than those in the 56-70 group. Zaks did not speculate about why the 56-70 age group had the highest titers. One possibility is that the small number of subjects in each group contributed to variability; the two oldest groups each contained 10 individuals and the youngest group contained 15. 

Zaks noted that the elderly are a high-risk population more susceptible to severe disease, and predicted that higher neutralization titers “will translate into better performance and more protection to these vulnerable people.”

In contrast to what appears to be a minimal decline in the antibody response to mRNA-1273, two other vaccines have shown steeper declines in early clinical studies.

Neutralizing titers induced by BNT162b2 from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX) fell by about 60% in subjects aged 65-85 years compared with 18-55 year-olds. Each cohort included 12 individuals. 

Ad5-nCoV from CanSino Biologics Inc. (HKEX:6185; Shanghai:688185), which produced somewhat weaker titers to begin with, showed a drop of 36% from 18-44 years to age 55 and up. The youngest cohort in CanSino’s trial enrolled 152 subjects; the 45-55 year-old cohort included 67 subjects and the oldest cohort included 34. 

Across age groups, the average titers induced by mRNA-1273 were were two to three times higher than those in convalescent sera obtained from 38 donors, about two thirds of whom had recovered from mild disease.

BNT162b2 produced titers in 18-55 year-olds that were 3.8 times higher than those in convalescent plasma; in 65-85 year-olds, the difference fell to 1.6 times higher. The convalescent sera used in the study also primarily came from mild patients (unhospitalized and symptomatic).

CanSino did not compare its vaccine titers to convalescent sera.

CanSino published data from a Phase II study in July in The Lancet. Pfizer and BioNTech reported their findings, from the Phase I portion of a Phase I/II/III study, a week ago in medRxiv (see “Triggering Immunogenicity in Older Patients”; “Pfizer, BioNTech Unveil Data for Lead Vaccine”).

T cell responses

Efficacy in humans has not yet been proven for any COVID-19 vaccine, and the threshold levels of neutralization antibodies needed to confer protection won’t be known until late-stage trials start to read out and one or more vaccines prove effective.

Another open question is whether and how much different T cell populations contribute to protection. 

For now, viral challenges studies in non-human primates offer the best clues to such correlates of protection. 

Several of these studies, including of mRNA-1273, suggest high neutralizing titers may be sufficient to confer protection, even in the absence of appreciable T cell activation (see “Non-human Primate Data Shed Light on Correlates of Protection”).

The animal data do not rule out protective contributions from T cells though, and Moderna also reported that 100 µg of mRNA-1273 induced Th1-biased CD4+ T cell responses that were consistent across the three age groups in the Phase I study.

CanSino has also shown its adenovirus vector vaccine stimulates T cells responses but did not stratify the data report by age. BioNTech and Pfizer did not evaluate T cell responses in their study.

Ad5-nCoV  has Military Specially-needed Drug Approval from China, which is valid for one year. And 30,000-volunteer pivotal trials of mRNA-1273 and BNT162b2 began in July (see “Two Lead Vaccines Enter Pivotal Testing”).

As of Tuesday, the Phase III COVE study of mRNA-1273 had enrolled just over half the target number of volunteers. On Thursday, Pfizer and BioNTech said over 11,000 patients had been enrolled in their pivotal trial.

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