In a new paper in the journal Nature, Barouch, Director of BIDMC’s Center for Virology and Vaccine Research, and colleagues shed light on the role of antibodies and immune cells in protection against SARS-CoV-2, the virus that causes COVID-19, in rhesus macaques. “In this study, we define the role of antibodies versus T cells in protection against COVID-19 in monkeys. We report that a relatively low antibody titer (the concentration of antibodies in the blood) is needed for protection,” said Barouch. “Such knowledge will be important in the development of next generation vaccines, antibody-based therapeutics, and public health strategies for COVID-19.”

Building on previous findings that SARS-CoV-2 infection protects rhesus monkeys from re-exposure, Barouch and colleagues purified and collected antibodies from animals that had recovered from infection. They administered the antibodies at various concentrations to 12 uninfected macaques and observed that protection against SARS-CoV-2 challenge was dose dependent. Animals that received higher amounts of antibodies were protected more completely, while animals that received lower amounts of antibodies were protected less well. Similarly, when the researchers administered various concentrations of the purified antibodies to 6 macaques with active SARS-CoV-2 infection, those given higher doses demonstrated more rapid viral control.

In a second set of experiments, Barouch and colleagues evaluated the role of specific immune cells — CD8+ T cells — in contributing to protection against the virus by removing these cells from animals that had recovered from SARS-CoV-2 infection. Removal of these immune cells left the animals vulnerable to infection after re-exposure to SARS-CoV-2.

“Our data define the role of antibodies and T cells in protection against COVID-19 in monkeys. Antibodies alone can protect, including at relatively low levels, but T cells are also helpful if antibody levels are insufficient,” said Barouch, who is also Professor of Medicine at Harvard Medical School, and a member of the Ragon Institute of MGH, MIT, and Harvard. “Such correlates of protection are important given the recent successful vaccine results from human trials, and the likelihood that these and other vaccines will become widely available in the spring; as a result future vaccines may need to be licensed based on immune correlates rather than clinical efficacy.”

Co-authors include co-first author Katherine McMahan, co-first author Jingyou Yu, co-first author Noe B. Mercado, co-first author Lisa H. Tostanoski, co-first author Abishek Chandrashekar, co-first author Jinyan Liu , co-first author Lauren Peter, Esther A. Bondzie, Gabriel Dagotto, Makda S. Gebre, Catherine Jacob-Dolan, Zhenfeng Li, Felix Nampanya, and Shivani Patel of BIDMC; co-first author Carolin Loos, Caroline Atyeo, Alex Zhu, and Galit Alter, of Ragon Institute of MGH, MIT, and Harvard; Laurent Pessaint, Alex Van Ry, Kelvin Blade, Jake Yalley-Ogunro, Mehtap Cabus, Renita Brown, Anthony Cook, Elyse Teow, Hanne Andersen, Mark G. Lewis, of Bioqual; and Douglas A. Lauffenburger of Massachusetts Institute of Technology.

This work was supported by the Ragon Institute of MGH, MIT, and Harvard, Mark and Lisa Schwartz Foundation, Massachusetts Consortium on Pathogen Readiness (MassCPR), the Bill & Melinda Gates Foundation (INV-006131), and the National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603, CA260476).

The authors declare no financial conflicts of interest. Barouch is a co-inventor on provisional SARS-CoV-2 vaccine patents (62/969,008; 62/994,630).

A study analyzing the reports was published today in the journal PLOS ONE. The study findings indicate that understanding and being aware of each threat is critical for managing and conserving killer whale populations. It also presents a baseline understanding of orca health.

The study was conducted by a team of marine mammal and orca specialists led by the British Columbia Ministry of Agriculture and coordinated through the SeaDoc Society, a Washington-based program of the University of California, Davis’ School of Veterinary Medicine. The lead author, Dr Stephen Raverty, and coauthor, Dr John Ford, are adjunct professions at the University of British Columbia Institute of Oceans and Fisheries and Department of Zoology, respectively.

The whales include those from healthy populations as well as endangered species, such as the southern resident whales regularly sighted off the coasts of British Columbia, Washington and Oregon.

Of 52 whales stranded between 2004 and 2013, causes of death were determined for 42 percent. For example, one calf died from sepsis following a halibut hook injury. Another starved from a congenital facial deformity. Two whales died from the blunt force trauma of vessel strikes. Additional causes of death include infectious disease and nutritional deficiencies.

‘We can do better’

Despite there being no singular common cause of death, the study found a common theme: Human-caused deaths occurred in every age class — from juveniles to subadults and adults.

“In British Columbia, we lost nine southern resident killer whales: 2 adults, 2 subadults and 1 calf died from trauma; one was a confirmed propeller strike, with one adult and two subadults from suspected ship strikes,” said lead author Stephen Raverty, a veterinarian pathologist with the BC Ministry of Agriculture and adjunct professor at UBC’s Institute for the Oceans and Fisheries. “One of these iconic species passed away from an infection secondary to satellite tagging. Another death was due to natural causes and the other two undetermined. Half of the southern killer whale deaths identified in this study were caused by human interactions.”

“Nobody likes to think we’re directly harming animals,” said co-author and SeaDoc Society Director Joe Gaydos, a wildlife veterinarian with the Karen C. Drayer Wildlife Health Center in the UC Davis School of Veterinary Medicine. “But it’s important to realize that we’re not just indirectly hurting them from things like lack of salmon, vessel disturbance or legacy toxins. It’s also vessel strikes and fish hooks. That humans are directly killing killer whales across all age classes is significant; it says we can do a better job.”

In 2004, Raverty and Graydos co-developed a standardized killer whale necropsy protocol. Revised in 2014 with help from Judy St. Leger, a pathologist working for SeaWorld, this guide helped improve examinations of deceased whales.

“The results from systematic necropsies of dead killer whales in this review is unique and will establish critical baseline information to assess future mitigation efforts,” Raverty said. “This work contributes to a better understanding of the impacts that ongoing human activities and environmental events have on killer whales.”

The authors acknowledge the report is an incomplete picture of orca health and mortality. Necropsies can only be performed on whales found in an adequate state to receive them, and even then, the cause of death cannot always be determined. But the report offers one of the most comprehensive looks yet at the multitude of human and environmental threats affecting killer whales and can help inform strategies to better protect them.

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So when a previously typical star’s behavior rapidly changes in a few decades, astronomers take note and get to work.

Such is the case with a star known as SAO 244567, which lies at the center of Hen 3-1357, commonly known as the Stingray Nebula. The Stingray Nebula is a planetary nebula — an expanse of material sloughed off from a star as it enters a new phase of old age and then heated by that same star into colorful displays that can last for up to a million years.

The tiny Stingray Nebula unexpectedly appeared in the 1980s and was first imaged by scientists in the 1990s using NASA’s Hubble Space Telescope. It is by far the youngest planetary nebula in our sky. A team of astronomers recently analyzed a more recent image of the nebula, taken in 2016 by Hubble, and found something unexpected: As they report in a paper accepted to the Astrophysical Journal, the Stingray Nebula has faded significantly and changed shape over the course of just 20 years.

If dimming continues at current rates, in 20 or 30 years the Stingray Nebula will be barely perceptible, and was likely already fading when Hubble obtained the first clear images of it in 1996, according to lead author Bruce Balick, an emeritus professor of astronomy at UW.

“This is an unprecedented departure from typical behavior for a planetary nebula,” said Balick. “Over time, we would expect it to imperceptibly brighten and expand, which could easily go unnoticed in a century or more. But here we’re seeing the Stingray nebula fade significantly in an incredibly compressed time frame of just 20 years. Moreover, its brightest inner structure has contracted — not expanded — as the nebula fades.”

Planetary nebulae form after most stars, including stars like our own sun, swell into red giants as they exhaust hydrogen fuel. At the end of the red giant phase, the star then expels large amounts of its outer material as it gradually — over the course of a million years — transforms into a small, compact white dwarf. The sloughed-off material expands outward for several thousand years while the star heats the material, which eventually becomes ionized and glows.

Balick and his co-authors, Martín Guerrero at the Institute of Astrophysics of Andalusia in Spain and Gerardo Ramos-Larios at the University of Guadalajara in Mexico, compared Hubble images of the Stingray Nebula taken in 1996 and 2016. Hen 3-1357 changed shape markedly over 20 years, losing the sharp, sloping edges that gave the Stingray Nebula its name. Its colors have faded overall and once-prominent blue expanses of gas near its center are largely gone.

“In a planetary nebula, the star is really the center of all the activity,” said Balick. “The material around it is directly responsive to the energy from its parent star.”

The team analyzed light spectra from Hen 3-1357 emitted by chemical elements in the nebula. Emission levels of hydrogen, nitrogen, sulfur and oxygen all dropped between 1996 and 2016, particularly oxygen, which dropped by a factor of 900. The resulting fade in color and the nebula’s change in shape are likely connected to the cooling of its parent star — from a peak of about 107,500 degrees Fahrenheit in 2002 to just under 90,000 degrees Fahrenheit in 2015 — which means it is giving off less ultraviolet ionizing radiation that heats the expelled gas and makes it glow.

“Like a doused forest fire, the smoke wanes more slowly than the flames that created it,” said Balick. “Even so, we were amazed when the Hubble images revealed how quickly the nebula was fading. It took a month of work to believe it.”

Astronomers have yet to understand why SAO 244567 made the Stingray Nebula light up and then fade almost as quickly. One theory, posited by a team led by Nicole Reindl at the University of Potsdam, is that the star underwent a brief burst of fresh helium fusion around its core, which stirred up its outer layers and caused its surface to both shrink and heat.

If so, then as its outer layers settle back down, the star may return to a more typical transition from red giant to white dwarf. Only future observations of the star and its nebula can confirm this.

“Unfortunately, the best tool to follow future changes in the Stingray Nebula, the Hubble Space Telescope, is near the end of its life as well,” said Balick. “We can hope, but the odds aren’t good for Hubble’s survival as its three remaining gyroscopes start to fail. It’s a good race to the finish.”

A new paper published in the Ecological Society of America’s journal Ecological Monographs addresses some of these questions. The findings reveal that the leaf microbiomes of sugar maple trees vary across the species’ range, changing in accordance with the types of trees in the surrounding “neighborhood.”

Geneviève Lajoie, now a post-doctoral researcher at the University of British Columbia and the paper’s lead author, performed the research as a Ph.D. student at the Université du Québec à Montréal. She and her field assistant spent a summer in hot pursuit of bacteria-covered foliage, camping at remote parks and rushing to get their leaf samples back to the lab for analysis before new conditions altered the leaves’ resident microbes.

The team sampled foliage at sites across Québec, Ontario and the northeastern United States. Lajoie’s analysis zeroed in on the iconic sugar maple — a species that is abundant at the southern end of the study range, but tapers off at more northern latitudes where conifers dominate the landscape. In fact, at the northern reaches of the study range, at sites like Monts-Valin National Park, sugar maples become anomalous enough that tracking them down among their evergreen neighbors was a challenge.

“To reach the site, we drove up north from Québec City and witnessed the gradual transition from the mixed deciduous forest of the Saint Lawrence Valley to a boreal landscape dominated by conifers,” Lajoie said. “Going sampling over the next days, we were looking for sugar maple populations — our focal species. Even though we knew it could be found in the park despite it being the northern limit of its range, encountering these beautiful trees seemingly out of place but still thriving were particularly amazing moments for me.”

However, despite being outliers on a conifer-dominated landscape, these northernmost sugar maple trees had adopted leaf microbiomes that blended in with their coniferous neighbors. LaJoie found a pattern along the latitudinal gradient of her study area: southern sugar maples, which are surrounded by lots of other sugar maples, tended to share a relatively similar microbiome — one that was distinct from other tree species in the area. But in more northern areas, where sugar maple trees are few and far between, the species hosted bacterial communities that resembled the microbiomes of other more dominant species.

The observations echo similar patterns that have been observed among animal microbiomes. Ground-dwelling animals, for instance, tend to have relatively similar microbiomes, possibly through increased contact with the feces of other animals, while canopy-dwelling animals have gut microbiomes that are less similar to each other.

While gut microbiomes are a hot research topic in the human health sciences, the forest phyllosphere remains a study system that is not well understood — and according to Lajoie, the fields of plant ecology and microbiology have been growing mostly in parallel for many years. This study’s findings provide a more complete picture of the plant-microbe relationship: what kinds of bacteria go on which trees, and how this pattern varies depending on how well a tree fits in with the crowd.

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