From the Frontlines of Pandemic Research; Omicron, Mandates, Prevention, and a Pancoronavirus Vaccine

Discovery; The Story from Southern Africa

The discovery of the Omicron variant in Southern Africa started with what experts call a “spike gene dropout.”

“It was identified by colleagues in Botswana and by our sequencers in South Africa,” explained Penny Moore, PhD. “We’d just been through a third wave in South Africa that was driven by the Delta variant. And what happened was a local diagnostic laboratory… started noticing an uptick in infections, and associated with that, they noticed that the diagnostic test that we routinely use was not performing optimally.”

Moore, a virologist at the University of the Witwatersrand, described the fast-moving sequence of events during a New York Academy of Sciences webinar on December 14. She explained that the PCR diagnostic test looked for four genetic markers typically found on the COVID-19 coronavirus. The tests in early November showed a reduced sensitivity; they were not detecting one of the targets. “That’s something we’d previously seen, with the Alpha variant in the UK,” Moore continued. “It’s called a spike gene drop out, or spike gene target failure.” It was a red flag.

“So that’s what led us in South Africa to start sequencing very deeply,” Moore explained. “We have a really excellent, next-generation genomics consortium here in South Africa, and they moved very rapidly to target those specific diagnostic samples that were behaving differently in the diagnostic tests. And that… showed us that we were dealing with a variant that had many, many more mutations that we were used to seeing in Delta.”

Moore, and her colleagues, soon were “being deluged in data” as they tried to answer questions from around the world about Omicron’s properties, including transmission rates, efficacy of vaccines, and whether the new strain causes more or less severe disease than others. As Moore earlier told Nature, “We’re flying at warp speed.”

Moore was one of four prominent scientists and public health officials participating in the webinar, What You Need to Know About Omicron and Future Coronavirus Variants. The others were: Rick Bright, PhD, who heads the Rockefeller Foundation’s Pandemic Prevention Institute; Dave A. Chokshi, MD, MSc, the Commissioner of the New York City Department of Health and Mental Hygiene; and Drew Weissman, MD, PhD, a pioneer in mRNA vaccine research at the University of Pennsylvania. The program was moderated by the Academy’s Melanie Brickman Borchard, PhD, MSc.

Moore’s work, and that of her colleagues, has drawn praise from around the world. “Timing and speed is absolutely essential for getting in front of an outbreak and for saving lives,” Bright told the panelists. “And I believe the world owes a debt of gratitude to the researchers in Southern Africa for immediately sharing this virus sequence with the global GISAID community, and for rapidly notifying their government and the word of this variant.” (GISAID is a global initiative that promotes the rapid sharing of genetic sequence and epidemiological data associated with human viruses.)

New York City; Fighting Back with Multiple Responses, Exactly One Year Later

“I want to start by just recognizing that we are on, precisely, the one year anniversary of our vaccination campaign,” said Chokshi. “It was December 14 of last year when the first person in the United States, Sandra Lindsay, a nurse in Queens, was vaccinated.” The day of the webinar also marked an escalation in New York City’s measures to tamp down the pandemic. It was the first day of a vaccine mandate for children aged 5 to 11 who engage in indoor public activities. “For New York City, we have about 160,000 children, five to 11, who are vaccinated with at least one dose so far,” Chokshi reported. “It’s a great start, but it’s only about a quarter of the total population.” He stressed that mask and vaccine mandates are only some of the tools at the city’s disposal: “We’re partnering with over 1,500 pediatrician offices. We’ve launched a school based vaccination clinic where we visited every single school that had children in that age range. And we have mobile vaccination units that are providing vaccination across the city.”

Chokshi said the city would be working hard to support pediatric vaccination in the new year, including the vaccination of younger children, which he said he hoped would be approved in the first quarter. He also said that as a public health official and the father of a two-and-a-half year old daughter, he is closely following an early report out of South Africa of an increase in very young children hospitalized with COVOD-19 infections.

While the Delta variant continues to circulate, and community spread of Omicron has begun in New York, Chokshi said he and his colleagues must address very human needs, as well as science. “You know, as we are entering the holidays, people are yearning of the social connection that the holidays bring, particularly given the trials and tribulations that we’ve all been through over the past, almost two years,” Chokshi said. “And, I think as public health professionals, we have to recognize, that that is where our fellow New Yorkers, our fellow human beings, are. And so my job, and our job, is to provide the guidance and the tools to be able to facilitate people celebrating as safely as they possibly can.”

A Pancoronavirus Vaccine

Weissman, a pioneer in the development of a core technology that makes the mRNA vaccines possible, shared some background and a status report on his current efforts to create what he calls a “pancoronavirus variant vaccine”. “If you look at coronaviruses, there have been three epidemics in the past 20 years, Weissman said. “That tells us there will be more. And we can do what we did for COVID-19, which is rush and make a vaccine. But it still shuts down the world for a year and a half.” Weissman’s research focuses on another approach, creating a vaccine that prevents transmission of all coronaviruses and their variants.

Weisman said his lab’s challenge is to identify “conserved regions” of genetic sequences shared by all coronaviruses, and to direct the immune response against those targets. In the lab, Weissman said his vaccine has been effective against “all of the current variants that have appeared, and will likely work against any variants that appear in the future.” Plans are underway to begin clinical trials within about a year.

Vaccine Hesitancy

Moore described mistrust of vaccines in many communities in South Africa, including among people who work in hospitals who have a very high rate of exposure to Sars-CoV-2. “I think the barriers are in many cases the same barriers that have been faced across the rest of the world,” she said. “There is a huge feeling of fear and helplessness in many of those communities and a lot of suspicion around vaccination… [T]here’s much talk in South Africa about the speed at which these vaccines have been developed. It’s something that we, as scientists, need to address very urgently. We need to explain that it may look like these vaccines have been develop really quickly, but it’s not true. You know, this comes out of decades and decades [of research].

Weissman spoke to the same issue:

I joke with people about this because had we taken two years or three years to develop the vaccine, they would've yelled at us that we were too slow. What people have to understand is that RNA vaccines have been studied for 25 years. They've been in clinical trials for almost 20 years. This is not brand new technology. The nucleoside modified mRNA LMPs [lipid mRNA particles] that we’ve developed, they've been in clinical trials for over five years before COVID 19 hit. So even this exact platform isn't new technology. What people have to understand is that no corners were cut in its development. What happened is the researchers, the pharmaceutical companies, the FDA, all got together and said, ‘how can we do these studies as fast as possible?’

The answer, Weissman said, was to conduct Phase 1, 2, and 3 clinical trials concurrently, rather than serially, which would have taken several years. “So there were no corners cut,” Weissman added. “More people were studied for COVID 19 than just about any other vaccine. It was done quickly because we have an emergency.”

Testing, Testing, Testing & Equity

Bright, who heads the Pandemic Prevention Institute at the Rockefeller Foundation, told the Academy audience that the emergency of Omicron could prompt necessary global, coordinated action— especially the expansion of testing—to control the pandemic.

“This virus has now taken hold of the human population,” Bright said, adding:

It is not going to go away on its own. We need to fight it with every tool that we have, vaccines, therapeutics, high quality masks, ventilation, air filtration, and implementing a robust testing strategy that can trigger effective contact tracing and rapid access to therapeutics. The question now for, for us, for me, is whether Omicron will remind the world of the urgency we face and drive us to real collaborative action.

The four experts all agreed a heightened focus on healthcare equity is necessary to control the pandemic. “Vaccine inequity is prolonging the COVID-19 pandemic and it’s jeopardizing all the progress that we’ve made to date,” Bright said, pointing out that that people who are unvaccinated remain significantly more likely to get sick from COVID-19, to pass it on to others, and to facilitate the emergence of new variants.

Chokshi said equity has been an important focus of efforts in New York City, especially in lowering barriers to access. This means bringing vaccines “into people’s communities, into their neighborhoods.” He cited as examples: “Partnering with federally-qualified heath centers. Moving to a decentralized approach where we use mobile sites, and also using in-home vaccination which is now available to anyone 12 and up across New York City.”

Another part of New York City’s efforts, Chokshi said, is building trust:

We worked on building vaccine confidence with our partners across New York City, knowing that government is one messenger, but that often it is not the most trusted messenger within communities. So we are partnering with faith leaders and community based organizations to build vaccine confidence.

Here is a recording of the complete webinar.

An important point that emerged in the December 14 discussion aligns closely with the mission of the Academy, that while science plays a central role in the global response to the pandemic, scientists must partner with members of many other communities, and with experts from many disciplines. “We have to also realize that science alone can’t keep us safe,” Bright said. “We need to ensure that governments and companies and communities, and even individuals such as ourselves, are working together. We’re sharing information, we’re making decisions based on science… to stop this outbreak.”

This type of collaborative effort is a goal of an important new Academy initiative, the International Science Reserve, or ISR. The project aims to mobilize scientists and critical resources in the face of future global crises, whether a new pandemic, a cyber attack, flooding, or a massive wildfire. Read about the ISR, here.

The Academy’s program on the Omicron variant was just the latest in a broad series starting early last year, all designed to help meet the need for unbiased, scientific information on Sar-CoV-2. Next in line is a symposium on March 30 and March 31, The Future of Vaccinology. The program will feature speakers from the Bill and Melinda Gates Research Institute, Pfizer, Novavax, and the Human Vaccines Project.