Published interim data show that all of the participants in the Phase I study of one of the most closely watched vaccines against the virus that causes Covid-19 developed immune system responses, at levels significantly higher than patients who had recovered.
Cambridge, Massachusetts-based Moderna said Tuesday that it had published the data on 45 participants, from the National Institute of Allergy and Infectious Diseases-sponsored study of the vaccine mRNA-1273, in the New England Journal of Medicine. Among the 15 participants who received the vaccine at the 100-microgram dose that the company plans to use in its Phase III trial, mean concentrations of neutralizing antibodies were 4.1 times higher than those seen in convalescent plasma from recovered Covid-19 patients when measured by the plaque reduction neutralization test (PRNT) and 2.1 times higher when measured by the pseudotyped lentivirus reporter single-round-of-infection neutralization assay (PsVNA). However, while encouraging, immune system responses do not indicate whether the vaccine will provide long-term protection.
Shares of Moderna rose as much as 19% above their Tuesday closing price in after-hours trading on the Nasdaq and were up nearly 15% in pre-market trading Wednesday morning during a conference call with company executives.
“These positive Phase I data are encouraging and represent an important step forward in the clinical development of mRNA-1273, our vaccine candidate against Covid-19, and we thank the NIH for their ongoing collaboration,” Moderna CEO Stephane Bancel said in a statement, referring to the National Institutes of Health. “The Moderna team continues to focus on starting our Phase III study this month and, if successful, filing a [Biologics License Application].”
Adverse events were described as mild to moderate and transient and occurred most notably at the 250-microgram dose level. In other dose groups, they tended to be more common after the second dose and occurred in all 15 participants in the 100-microgram group. The most commonly reported events included fatigue, chills, headache and myalgia, along with injection site pain.
One potentially encouraging sign is that the vaccine elicited T-cell responses of the sort that could mitigate the potential for enhanced respiratory disease, or ERD, which has been an ongoing concern with vaccines against coronaviruses, based on animal studies of vaccines against the severe acute respiratory syndrome and Middle East respiratory syndrome viruses. ERD occurs when people who have been vaccinated against a respiratory disease nevertheless experience it more severely as a result of a CD4 T-cell response biased in favor of the cytokine Th2 and was observed in a respiratory syncytial virus vaccination program in the late 1960s. Nevertheless, Moderna said mRNA-1273 provoked Th1-biased CD4 cell responses without elevations of Th2-biased responses, thus potentially assuaging such concerns.
“Further, the CD4 response has correlated with antibody titers in recovered patients, suggesting that the vaccine is delivering a similar response as the natural immune system,” Morgan Stanley analyst Matthew Harrison wrote in a note to investors.
The company plans to start its Phase III COVE trial on July 27, under collaboration with the federal government’s Operation Warp Speed program. A page for the randomized, placebo-controlled trial, which will enroll up to 30,000 participants, has been posted on ClinicalTrials.gov. The page lists 87 trial locations, all in the U.S.
Harrison noted that both the Moderna and Pfizer/BioNTech vaccines elicit neutralizing antibody responses above those of recovered patients. However, that may be easier to accomplish with the latter because it targets the receptor-binding domain of the virus, as opposed to the entire spike protein, which mRNA-1273 targets.
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