A Look Back at Science’s 2022 Breakthroughs
Posted on by Lawrence Tabak, D.D.S., Ph.D.
Happy New Year! I hope everyone finished 2022 with plenty to celebrate, whether it was completing a degree or certification, earning a promotion, attaining a physical fitness goal, or publishing a hard-fought scientific discovery.
If the latter, you are in good company. Last year produced some dazzling discoveries, and the news and editorial staff at the journal Science kept a watchful eye on the most high-impact advances of 2022. In December, the journal released its list of the top 10 advances across the sciences, from astronomy to zoology. In case you missed it, Science selected NASA’s James Webb Space Telescope (JWST) as the 2022 Breakthrough of the Year .
This unique space telescope took 20 years to complete, but it has turned out to be time well spent. Positioned 1.5-million-kilometers from Earth, the JWST and its unprecedented high-resolution images of space have unveiled the universe anew for astronomers and wowed millions across the globe checking in online. The telescope’s image stream, beyond its sheer beauty, will advance study of the early Universe, allowing astronomers to discover distant galaxies, explore the early formation of stars, and investigate the possibility of life on other planets.
While the biomedical sciences didn’t take home the top prize, they were well represented among Science’s runner-up breakthroughs. Some of these biomedical top contenders also have benefited, directly or indirectly, from NIH efforts and support. Let’s take a look:
RSV vaccines nearing the finish line: It’s been one of those challenging research marathons. But scientists last year started down the homestretch with the first safe-and-effective vaccine for respiratory syncytial virus (RSV), a leading cause of severe respiratory illness in the very young and the old.
In August, the company Pfizer presented evidence that its experimental RSV vaccine candidate offered protection for those age 60 and up. Later, they showed that the same vaccine, when administered to pregnant women, helped to protect their infants against RSV for six months after birth. Meanwhile, in October, the company GSK announced encouraging results from its late-stage phase III trial of an RSV vaccine in older adults.
As Science noted, the latest clinical progress also shows the power of basic science. For example, researchers have been working with chemically inactivated versions of the virus to develop the vaccine. But these versions have a key viral surface protein that changes its shape after fusing with a cell to start an infection. In this configuration, the protein elicits only weak levels of needed protective antibodies.
Back in 2013, Barney Graham, then with NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and colleagues, solved the problem . Graham’s NIH team discovered a way to lock the protein into its original prefusion state, which the immune system can better detect. This triggers higher levels of potent antibodies, and the discovery kept the science—and the marathon—moving forward.
These latest clinical advances come as RSV and other respiratory viruses, including SARS-CoV-2, the cause of COVID-19, are sending an alarming number of young children to the hospital. The hope is that researchers will cross the finish line this year or next, and we’ll have the first approved RSV vaccine.
Virus fingered as cause of multiple sclerosis: Researchers have long thought that multiple sclerosis, or MS, has a viral cause. Pointing to the right virus with the required high degree of certainty has been the challenge, slowing progress on the treatment front for those in need. As published in Science last January, Alberto Ascherio, Harvard T.H. Chan School of Public Health, Boston, and colleagues produced the strongest evidence yet that MS is caused by the Epstein-Barr virus (EBV), a herpesvirus also known for causing infectious mononucleosis .
The link between EBV and MS had long been suspected. But it was difficult to confirm because EBV infections are so widespread, and MS is so disproportionately rare. In the recent study, the NIH-supported researchers collected blood samples every other year from more than 10 million young adults in the U.S. military, including nearly 1,000 who were diagnosed with MS during their service. The evidence showed that the risk of an MS diagnosis increased 32-fold after EBV infection, but it held steady following infection with any other virus. Levels in blood serum of a biomarker for MS neurodegeneration also went up only after an EBV infection, suggesting that the viral illness is a leading cause for MS.
Further evidence came last year from a discovery published in the journal Nature by William Robinson, Stanford University School of Medicine, Stanford, CA, and colleagues. The NIH-supported team found a close resemblance between an EBV protein and one made in the healthy brain and spinal cord . The findings suggest an EBV infection may produce antibodies that mistakenly attack the protective sheath surrounding our nerve cells. Indeed, the study showed that up to one in four people with MS had antibodies that bind both proteins.
This groundbreaking research suggests that an EBV vaccine and/or antiviral drugs that thwart this infection might ultimately prevent or perhaps even cure MS. Of note, NIAID launched last May an early-stage clinical trial for an experimental EBV vaccine at the NIH Clinical Center, Bethesda, MD.
AI Gets Creative: Science’s 2021 Breakthrough of the Year was AI-powered predictions of protein structure. In 2022, AI returned to take another well-deserved bow. This time, Science singled out AI’s now rapidly accelerating entry into once uniquely human attributes, such as artistic expression and scientific discovery.
On the scientific discovery side, Science singled out AI’s continued progress in getting creative with the design of novel proteins for vaccines and myriad other uses. One technique, called “hallucination,” generates new proteins from scratch. Researchers input random amino acid sequences into the computer, and it randomly and continuously mutates them into sequences that other AI tools are confident will fold into stable proteins. This greatly simplifies the process of protein design and frees researchers to focus their efforts on creating a protein with a desired function.
AI research now engages scientists around world, including hundreds of NIH grantees. Taking a broader view of AI, NIH recently launched the Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) Program. It will help to create greater diversity within the field, which is a must. A lack of diversity could perpetuate harmful biases in how AI is used, how algorithms are developed and trained, and how findings are interpreted to avoid health disparities and inequities for underrepresented communities.
And there you have it, some of the 2022 breakthroughs from Science‘s news and editorial staff. Of course, the highlighted biomedical breakthroughs don’t capture the full picture of research progress. There were many other milestone papers published in 2022 that researchers worldwide will build upon in the months and years ahead to make further progress in their disciplines and, for some, draw the attention of Science’s news and editorial staff. Here’s to another productive year in biomedical research, which the blog will continue to feature and share with you as it unfolds in 2023.
 2022 Breakthrough of the Year. Science. Dec 15, 2022.
 Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. McLellan JS, Chen M, Leung S, Kwong PD, Graham BS, et al. Science. 2013 May 31;340(6136):1113-1117.
 Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, Elledge SJ, Niebuhr DW, Scher AI, Munger KL, Ascherio A. Science. 2022 Jan 21;375(6578):296-301.
 Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM. Lanz TV, Brewer RC, Steinman L, Robinson WH, et al. Nature. 2022 Mar;603(7900):321-327.
Respiratory Syncytial Virus (RSV) (National Institute of Allergy and Infectious Diseases/NIH)
Multiple Sclerosis (National Institute of Neurological Disorders and Stroke/NIH)
Barney Graham (Morehouse School of Medicine, Atlanta)
Alberto Ascherio (Harvard T.H. Chan School of Public Health, Boston)
Robinson Lab (Stanford Medicine, Stanford, CA)
Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) Program (NIH)
James Webb Space Telescope (Goddard Space Flight Center/NASA, Greenbelt, MD)
How COVID-19 Immunity Holds Up Over Time
Posted on by Lawrence Tabak, D.D.S., Ph.D.
More than 215 million people in the United States are now fully vaccinated against the SARS-CoV-2 virus responsible for COVID-19 . More than 40 percent—more than 94 million people—also have rolled up their sleeves for an additional, booster dose. Now, an NIH-funded study exploring how mRNA vaccines are performing over time comes as a reminder of just how important it will be to keep those COVID-19 vaccines up to date as coronavirus variants continue to circulate.
The results, published in the journal Science Translational Medicine, show that people who received two doses of either the Pfizer or Moderna COVID-19 mRNA vaccines did generate needed virus-neutralizing antibodies . But levels of those antibodies dropped considerably after six months, suggesting declining immunity over time.
The data also reveal that study participants had much reduced protection against newer SARS-CoV-2 variants, including Delta and Omicron. While antibody protection remained stronger in people who’d also had a breakthrough infection, even that didn’t appear to offer much protection against infection by the Omicron variant.
The new study comes from a team led by Shan-Lu Liu at The Ohio State University, Columbus. They wanted to explore how well vaccine-acquired immune protection holds up over time, especially in light of newly arising SARS-CoV-2 variants.
This is an important issue going forward because mRNA vaccines train the immune system to produce antibodies against the spike proteins that crown the surface of the SARS-CoV-2 coronavirus. These new variants often have mutated, or slightly changed, spike proteins compared to the original one the immune system has been trained to detect, potentially dampening the immune response.
In the study, the team collected serum samples from 48 fully vaccinated health care workers at four key time points: 1) before vaccination, 2) three weeks after the first dose, 3) one month after the second dose, and 4) six months after the second dose.
They then tested the ability of antibodies in those samples to neutralize spike proteins as a correlate for how well a vaccine works to prevent infection. The spike proteins represented five major SARS-CoV-2 variants. The variants included D614G, which arose very soon after the coronavirus first was identified in Wuhan and quickly took over, as well as Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529).
The researchers explored in the lab how neutralizing antibodies within those serum samples reacted to SARS-CoV-2 pseudoviruses representing each of the five variants. SARS-CoV-2 pseudoviruses are harmless viruses engineered, in this case, to bear coronavirus spike proteins on their surfaces. Because they don’t replicate, they are safe to study without specially designed biosafety facilities.
At any of the four time points, antibodies showed a minimal ability to neutralize the Omicron spike protein, which harbors about 30 mutations. These findings are consistent with an earlier study showing a significant decline in neutralizing antibodies against Omicron in people who’ve received the initial series of two shots, with improved neutralizing ability following an additional booster dose.
The neutralizing ability of antibodies against all other spike variants showed a dramatic decline from 1 to 6 months after the second dose. While there was a marked decline over time after both vaccines, samples from health care workers who’d received the Moderna vaccine showed about twice the neutralizing ability of those who’d received the Pfizer vaccine. The data also suggests greater immune protection in fully vaccinated healthcare workers who’d had a breakthrough infection with SARS-CoV-2.
In addition to recommending full vaccination for all eligible individuals, the Centers for Disease Control and Prevention (CDC) now recommends everyone 12 years and up should get a booster dose of either the Pfizer or Moderna vaccines at least five months after completing the primary series of two shots . Those who’ve received the Johnson & Johnson vaccine should get a booster at least two months after receiving the initial dose.
While plenty of questions about the durability of COVID-19 immunity over time remain, it’s clear that the rapid deployment of multiple vaccines over the course of this pandemic already has saved many lives and kept many more people out of the hospital. As the Omicron threat subsides and we start to look forward to better days ahead, it will remain critical for researchers and policymakers to continually evaluate and revise vaccination strategies and recommendations, to keep our defenses up as this virus continues to evolve.
 COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention. February 27, 2022.
 Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection. Evans JP, Zeng C, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Sci Transl Med. 2022 Feb 15:eabn8057.
 COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Feb 2, 2022.
COVID-19 Research (NIH)
Shan-Lu Liu (The Ohio State University, Columbus)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development
Latest on Omicron Variant and COVID-19 Vaccine Protection
Posted on by Dr. Francis Collins
There’s been great concern about the new Omicron variant of SARS-CoV-2, the coronavirus that causes COVID-19. A major reason is Omicron has accumulated over 50 mutations, including about 30 in the spike protein, the part of the coronavirus that mRNA vaccines teach our immune systems to attack. All of these genetic changes raise the possibility that Omicron could cause breakthrough infections in people who’ve already received a Pfizer or Moderna mRNA vaccine.
So, what does the science show? The first data to emerge present somewhat encouraging results. While our existing mRNA vaccines still offer some protection against Omicron, there appears to be a significant decline in neutralizing antibodies against this variant in people who have received two shots of an mRNA vaccine.
However, initial results of studies conducted both in the lab and in the real world show that people who get a booster shot, or third dose of vaccine, may be better protected. Though these data are preliminary, they suggest that getting a booster will help protect people already vaccinated from breakthrough or possible severe infections with Omicron during the winter months.
Though Omicron was discovered in South Africa only last month, researchers have been working around the clock to learn more about this variant. Last week brought the first wave of scientific data on Omicron, including interesting work from a research team led by Alex Sigal, Africa Health Research Institute, Durban, South Africa .
In lab studies working with live Omicron virus, the researchers showed that this variant still relies on the ACE2 receptor to infect human lung cells. That’s really good news. It means that the therapeutic tools already developed, including vaccines, should generally remain useful for combatting this new variant.
Sigal and colleagues also tested the ability of antibodies in the plasma from 12 fully vaccinated individuals to neutralize Omicron. Six of the individuals had no history of COVID-19. The other six had been infected with the original variant in the first wave of infections in South Africa.
As expected, the samples showed very strong neutralization against the original SARS-CoV-2 variant. However, antibodies from people who’d been previously vaccinated with the two-dose Pfizer vaccine took a significant hit against Omicron, showing about a 40-fold decline in neutralizing ability.
This escape from immunity wasn’t complete. Indeed, blood samples from five individuals showed relatively good antibody levels against Omicron. All five had previously been infected with SARS-CoV-2 in addition to being vaccinated. These findings add to evidence on the value of full vaccination for protecting against reinfections in people who’ve had COVID-19 previously.
Also of great interest were the first results of the Pfizer study, which the company made available in a news release . Pfizer researchers also conducted laboratory studies to test the neutralizing ability of blood samples from 19 individuals one month after a second shot compared to 20 others one month after a booster shot.
These studies showed that the neutralizing ability of samples from those who’d received two shots had a more than 25-fold decline relative to the original virus. Together with the South Africa data, it suggests that the two-dose series may not be enough to protect against breakthrough infections with the Omicron variant.
In much more encouraging news, their studies went on to show that a booster dose of the Pfizer vaccine raised antibody levels against Omicron to a level comparable to the two-dose regimen against the original variant (as shown in the figure above). While efforts already are underway to develop an Omicron-specific COVID-19 vaccine, these findings suggest that it’s already possible to get good protection against this new variant by getting a booster shot.
Very recently, real-world data from the United Kingdom, where Omicron cases are rising rapidly, are providing additional evidence for how boosters can help. In a preprint , Andrews et. al showed the effectiveness of two shots of Pfizer mRNA vaccine trended down after four months to about 40 percent. That’s not great, but note that 40 percent is far better than zero. So, clearly there is some protection provided.
Most impressively (as shown in the figure from Andrews N, et al.) a booster substantially raised that vaccine effectiveness to about 80 percent. That’s not quite as high as for Delta, but certainly an encouraging result. Once again, these data show that boosting the immune system after a pause produces enhanced immunity against new viral variants, even though the booster was designed from the original virus. Your immune system is awfully clever. You get both quantitative and qualitative benefits.
It’s also worth noting that the Omicron variant mostly doesn’t have mutations in portions of its genome that are the targets of other aspects of vaccine-induced immunity, including T cells. These cells are part of the body’s second line of defense and are generally harder for viruses to escape. While T cells can’t prevent infection, they help protect against more severe illness and death.
It’s important to note that scientists around the world are also closely monitoring Omicron’s severity While this variant appears to be highly transmissible, and it is still early for rigorous conclusions, the initial research indicates this variant may actually produce milder illness than Delta, which is currently the dominant strain in the United States.
But there’s still a tremendous amount of research to be done that could change how we view Omicron. This research will take time and patience.
What won’t change, though, is that vaccines are the best way to protect yourself and others against COVID-19. (And these recent data provide an even-stronger reason to get a booster now if you are eligible.) Wearing a mask, especially in public indoor settings, offers good protection against the spread of all SARS-CoV-2 variants. If you’ve got symptoms or think you may have been exposed, get tested and stay home if you get a positive result. As we await more answers, it’s as important as ever to use all the tools available to keep yourself, your loved ones, and your community happy and healthy this holiday season.
 SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. Sandile C, et al. Sandile C, et al. medRxiv preprint. December 9, 2021.
 Pfizer and BioNTech provide update on Omicron variant. Pfizer. December 8, 2021.
 Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. Andrews N, et al. KHub.net preprint. December 10, 2021.
COVID-19 Research (NIH)
Sigal Lab (Africa Health Research Institute, Durban, South Africa)