In a previous blog we discussed the ongoing clinical studies about the development of a safe and effective vaccine against the virus producing the Covid-19 infection. Thanks to the decades-old research efforts to design and develop a vaccine against AIDS—so far without results due to the complexity and mutations of that virus—there was a significant body of scientific work by the time the SARS-CoV-2 genome was published on March 16, 2020. Immediately several groups started working on the vaccine development and a few of them—counting on the “generous” pockets of Big Pharma and Uncle Sam—could even develop the industrial capacity in a parallel way to make the process faster.
The biotechnology company Moderna, located in Cambridge, Massachusetts, teamed up with the National Institute of Allergy and Infectious Diseases (NIAID) to create a novel vaccine candidate that uses a tiny bit of messenger RNA from the infecting virus to provoke an immunological response in the host. The researchers recently published an initial report in the New England Journal of Medicine. They said that: “The candidate vaccine mRNA-1273 is a lipid nonparticle-encapsulated, nucleoside-modified messenger RNA (mRNA)-based vaccine that encodes the SARS-VoV-2 spike (S) glycoprotein stabilized in its prefusion conformation.” The basic idea is to safely get a tiny amount of highly coated virus mRNA inside a living being to elicit an immunological response without triggering symptoms like respiratory distress. “The mRNA-1273 vaccine candidate, manufactured by Moderna, encodes the S-2P antigen, consisting of the SARS-CoV-2 glycoprotein with a transmembrane anchor and an intact S1-S2 cleavage site.”
The researchers have developed a phase 1-dose escalation-open clinical trial in the Kaiser Permanente Washington Health Research Institute in Seattle and Emory University School of Medicine in Atlanta. The 45 participants were healthy adults whose age ranged from 18 to 55 years of age that received two injections of trial vaccine 28 days apart at dosages of 25 ug, 100 ug or 250 ug; they were not previously vetted for the presence of the SARS-CoV-2. The deltoid muscle was injected with 0.% ml on days 1 and 29; follow-up visits were scheduled at days 7 and 14, after each vaccination plus four other appointments, being 394 the last one. For safety reasons there were four sentinel participants in the 25-ug group followed by four others in the 100-ug group. The participants were charged with recording any local and systemic symptoms and could not use acetaminophen or similar drugs.
There were no serious adverse effects in all the participants except in one of them who developed a transient urticaria after the first vaccination and had to withdraw. None of them reported fever after the first dose; after the second dose, none of the participants in the 25-ug reported feverish symptoms. In the 100-ug group, 6 participants had fever and in the 250-ug group 8 did—only one had severe fever. “Binding antibody IgG geometric mean titers (GMTs) to S-2p increased rapidly after the first vaccination, with seroconversion in all participants by day 15. Dose-dependent responses were evident. For both assays, the median magnitude of antibody responses after the first vaccination in the 100-ug and 250-ug dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens.” The titers of both binding and neutralizing antibodies produced by the vaccine were similar to the ones found in the convalescent serum of patients that had been infected by the SARS-CoV-2. They found that S-P2—the antigen inside the vaccine—induced the activation of high-quality functional antibody responses and Th1-biased T-cells that block the replication of the virus in the respiratory system—one of the leading causes of death.
The researchers considered that the 100-ug dose of the mRNA-1273 vaccine is the best shot to neutralize the virus and at the same time promote the activation of the immunological system. In a CNN interview, Dr. Tal Zaks, Moderna‘s Chief Medical Officer, said that they need to make sure that the benefit/risk ratio of the vaccine candidate warrants its deployment in a population that is still largely free of the virus. They have recruited thousands of volunteers for a big phase 3 efficacy trial this month.
Last April Moderna received U$ 472 million from the U.S. government’s Biomedical Advanced Research and Development Authority (BARDA) to contribute financially for the development of their promising vaccine. On July 26 the company announced that it had received an additional U$ 472 million to prop their project. As we said in a previous blog, the governments of the richest countries are already positioning themselves for the pole position to claim priority for the precious vials of a functioning vaccine. Less financially endowed countries (like Argentina, Brazil and South Africa) that also have a significant pool of qualified scientists and a basic Public Health infrastructure became enthusiastic hosts of the trials (providing volunteers and services) to leapfrog to the queue’s front.
On July 27, both Moderna Inc. and Pfizer Inc. announced the start of their decisive and separate clinical trials that will involve thousands of participants in many countries.
May God Almighty grant wisdom and determination to these researchers and volunteers.
Note. The featured image is a reproduction of the oil painting of William Jenner, the English physician that designed the smallpox vaccine in the early 19th century.
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