The announcement Monday that a vaccine developed by Moderna and the federal government is 94.5 percent effective raised hopes for an eventual slowdown in COVID-19 transmission but questions remain about how long protection lasts and how long it will take to vaccinate enough Americans to stop the virus' widescale spread.
“Ninety-five percent was aspirational. Our aspirations have been met, and that’s very good news,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
The news follows similar interim results from Pfizer and BioNTech, which announced last Monday that its vaccine showed 90 percent efficacy in interim results.
The massive Moderna clinical trial involves more than 30,000 U.S. participants. Of the 95 people in the trial who got sick with COVID-19, 90 people had received the placebo, while five people had received the vaccine.
Side effects among those receiving the vaccine were mild or moderate, the drugmaker said, including pain or redness around the shot, fatigue, myalgia, arthralgia and headache.
The mRNA-1273 vaccine was co-developed by Moderna and the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The drugmaker and government scientists met on Zoom to discuss progress every Saturday morning.
Both the drugmaker and the government were “blinded” to the results until an independent data and safety monitoring board reviewed the clinical trial data and shared them with Moderna, NIH and other federal officials Sunday.
The drugmaker still must submit the data to the Food and Drug Administration, which will consider whether to make the vaccine available through an emergency use authorization. The data will also be reviewed by another group of independent scientists that advises FDA on whether to approve vaccines, the Vaccines and Related Biological Products Advisory Committee.
The Moderna vaccine’s promising results are a return on billions of dollars in public investment. Operation Warp Speed — the joint venture between the departments of Defense and Health and Human Services on COVID-19 vaccine and therapeutics development — invested $1 billion for research and development and $1.5 billion for manufacturing and delivery.
Federal funding makes up 100 percent of the vaccine’s development money, according to a disclosure Moderna made as a condition of one of its government contracts.
Still, Moderna has indicated it expects to profit from the vaccine. Moderna executives including CEO Stéphane Bancel, Chief Medical Officer Tal Zaks and President Stephen Hoge have sold tens of millions of dollars of stock.
Government scientists like Fauci and NIH Director Francis Collins and Moderna’s executives emphasized on a call Monday that the clinical trial participants are representative of the general public. To ensure a vaccine is efficacious in the general public, participants in the clinical trial should reflect the population at large.
Bancel told reporters that 11 of the people in the clinical trial got sick with severe disease, and they were all in the placebo group.
The FDA only requires that drugmakers prove the vaccine is effective at staving off moderate disease, because proving efficacy against severe disease would be logistically very difficult, but the agency’s outside advisors with VRBPAC have expressed they would like to see more evidence vaccines can help those most at risk of dying.
Hoge said that 42 percent of clinical trial participants were at risk of severe disease because they were over the age of 65 years old or had a co-morbid condition that can exacerbate COVID-19 like diabetes or asthma.
The clinical trial participants also include 37 percent of trial volunteers from racial and ethnic minorities. Surgeon General Jerome Adams last month said the government’s Saturday morning discussions with the drugmaker often centered on how to enroll more Black participants.
The more effective a vaccine is, the easier it is to reach herd immunity and resume pre-pandemic life. But a number of questions remain to be answered and distribution challenges must be overcome before that is achieved.
Moderna’s clinical trial began recruiting participants in late July, so there is only evidence thus far that people who received the vaccine have protection for a few months. Some infectious diseases experts worry that the fabulous efficacy results could reflect a temporary “plasma blast” that wanes over time.
The topline efficacy results of 94.5 percent Moderna’s vaccine and 90 percent efficacy in Pfizer’s vaccine have “been blown completely out of proportion in terms of what we actually know that means,” according to Michael Mina, a Harvard Center for Communicable Disease Dynamics professor.
“When somebody first gets vaccinated, your body has a natural part of its process that creates a huge number of plasma blasts. These are by definition temporary cells. They live in the blood and create huge numbers of antibodies,” Mina said on a call Friday.
“The scale we have evaluated the beneficial effect of these vaccines unfortunately matches the life span of these temporary cells that have to, by definition, die off,” Mina continued. “Is the 90 percent efficacy within the first few months driven entirely by this massive explosion of antibodies that are temporary? At three to six months, or six to 12 months range, are we still going to see that same level of protection once those plasma blasts die off and fall away?”
Fauci responded to that concern on the call Monday.
“When you vaccinate someone with anything, any kind of an antigen or immunogen, what you see are these activated cells called plasma blasts which can make antibody. When those cells diminish…, they are replaced with memory B-cells in addition to some T-cell response. The durability of immunity relies on the memory B-cells,” said Fauci. “We do not know at this point what the durability of protection will be.”
Distribution could also be a challenge for any vaccine the FDA authorizes. Advocates for public health agencies say an additional $8.4 billion in investment is needed for the historic challenge. Congress does not appear close to providing this money.
Convincing enough people to get vaccinated to slow the spread also could delay the resumption of some normal activities, public health experts say.
Maintaining a cold enough temperature to ensure the vaccine is stable could also pose a challenge. Moderna’s vaccine must be stored at sub-zero temperatures but is not as sensitive as Pfizer’s, which the company said requires storage at 103 degrees Fahrenheit below zero. Moderna’s vaccine can be stored in a standard freezer for up to 30 days.
Moderna says that if authorized by FDA, the vaccine could be available to 10 million people by the end of the year.