News Listing

Dear Colleagues:

With great sadness, I write to inform you of the sudden passing of Dr. James Champoux, professor and former chair of the UW School of Medicine Department of Microbiology. He died on Monday [May 13, 2019], a week after being diagnosed with pancreatic cancer, at the age of 76.

Dr. Champoux was appointed department chair in October 2007, after serving twice before as interim chair, and he continued in that role until earlier this year. He was dedicated to his colleagues, truly generous in his service to the School of Medicine, and justifiably proud to lead one of the premier biological science departments in the country.

The Department of Microbiology has a national reputation for high-quality teaching and an international reputation for excellence in research. In the most recent U.S. News & World Report rankings, the department is No. 2 in the nation for best graduate programs in microbiology and No. 4 in the world among global universities.

A Seattle native, Dr. Champoux was part of the first group of students admitted to the University of Washington Honors Program when it was founded in 1961. After graduating with a major in chemistry, he completed his doctorate degree in biochemistry at Stanford University in 1970.

Dr. Champoux’s early career coincided with the biology revolution that began in the 1970s — a time when rapid advances in microbiology and the development of biotechnology were starting to increase our understanding of all living systems. He made his first contribution to this revolution during a postdoctoral fellowship at the Salk Institute in San Diego when he discovered an enzyme called DNA topoisomerase I while working with Nobel Prize recipient Renato Dulbecco.

When Dr. Champoux returned home to join the UW Department of Microbiology faculty in 1972, he embarked on an illustrious academic career that continued for the next 47 years. During this time, he made major contributions to our understanding of oncogenesis and viral infections through his research on enzymes and retroviruses.

Dr. Champoux published more than 125 papers, and he was recognized with numerous honors, including a Guggenheim Fellowship (1980-81) and the prestigious NIH Merit Award (1998). He was elected by his peers to be a fellow of the American Academy of Microbiology (2005) and a member of the Washington State Academy of Sciences (2010). More recently, he was named a fellow of the American Association for the Advancement of Science (2017).

As department chair, Dr. Champoux recruited six new faculty members and worked to increase diversity among our faculty and graduate students. He was committed to excellence in education and exemplified this important faculty role as a wonderful teacher of undergraduate and graduate students. In 1985, he won the UW Distinguished Teaching Award.

The news of Dr. Champoux’s unexpected passing has been received by all of his colleagues with shock and sadness. On their behalf, I want to extend our deepest sympathies to his wife, Sharon, and daughter, Katie, on their profound loss. We are very fortunate that Dr. Champoux chose to spend his faculty career in the Department of Microbiology. He will be greatly missed.

 

Sincerely,

Paul G. Ramsey, M.D. 
CEO, UW Medicine 
Executive Vice President for Medical Affairs and 
Dean of the School of Medicine, 
University of Washington

This article describes the recent FDA approval of the anti-TB agent pretomanid, and it’s use in a novel regimen that is saving lives of multiply-drug resistant (MDR) TB patients in South Africa. Department of Microbiology Professor and Chair David Sherman played a major role in the early stage development of pretomanid.

Fang Lab Members publish in Cell Host and Microbe:

 

Salmonella enterica serovar Typhi causes typhoid fever only in humans. Murine infection with S. Typhimurium is used as a typhoid model, but its relevance to human typhoid is limited. Non-obese diabetic-scid IL2rγnull mice engrafted with human hematopoietic stem cells (hu-SRC-SCID) are susceptible to lethal S. Typhi infection. In this study, we use a high-density S. Typhi transposon library in hu-SRC-SCID mice to identify virulence loci using transposon-directed insertion site sequencing (TraDIS). Vi capsule, lipopolysaccharide (LPS), and aromatic amino acid biosynthesis were essential for virulence, along with the siderophore salmochelin. However, in contrast to the murine S. Typhimurium model, neither the PhoPQ two-component system nor the SPI-2 pathogenicity island was required for lethal S. Typhi infection, nor was the CdtB typhoid toxin. These observations highlight major differences in the pathogenesis of typhoid and non-typhoidal Salmonellainfections and demonstrate the utility of humanized mice for understanding the pathogenesis of a human-specific pathogen.

Dr Rudy Urbano, a recent graduate of our program, has just been awarded a prestigious Hanna Gray Fellowship from the Howard Hughes Medical Institute. Dr Urbano was a member of Dr Ferric Fang's Lab and defended in Autumn 2017. 

Prof. Daniel Wozniak, Prof Doriano Lamba and UW Microbiology's own Dr Matt Parsek were awarded the XXVII International
Prize "Saint Francis and Claire of Assisi" -  Science and Research section for our collaborative work on biofilm matrix proteins.

Dr. Michael Lagunoff was elected as a fellow of the American Association for the Advancement of Science (AAAS fellow).  The council elects members whose “efforts on behalf of the advancement of science or its applications are scientifically or socially distinguished”. Dr. Lagunoff was honored “for contributions to how viral infections cause cancer including demonstration that Kaposi’s Sarcoma herpesvirus activates oncogenic cell signaling pathways”.  He will receive his award in February as part of the Associations annual meeting.

All Microbiology classes will be taught online effective 3/9/20 through the end of Winter quarter. Please visit your class canvas page or contact your instructors for information on how to connect to online classrooms via Zoom. UW plans to resume normal class operations when the spring quarter begins March 30, pending public health guidance. UW provides daily updates and FAQs on COVID-19.

 

How the retired professor and department chair continues shaping the field — and UW Medicine.

It’s a Friday afternoon, but Eugene Nester, PhD, is still in the office. Although he’s retired, the professor emeritus of microbiology comes in regularly to review grant proposals and read up for his science discussion group — everything from math to oceanography. If he’s not in his office, you might find him volunteering at the Burke Museum, learning about dinosaurs or Native American basketry in order to answer visitors’ questions. Nester’s irrepressible curiosity has always led him to explore other disciplines, a habit that has served him well throughout a long and successful career.

A lifelong love of microbiology
Nester first became interested in microbiology in his teens, partly influenced by popular books like Arrowsmith and Microbe Hunters. “They influenced a lot of people who ended up going into microbiology by pointing out just how exciting a field it was,” says Nester.

After graduating with a bachelor’s degree in microbiology from Cornell, Nester was drafted into a biological warfare unit of the U.S. Army. Before his military service, he had planned to study food microbiology at graduate school in Wisconsin, but after his discharge, he decided to study genetics and biochemistry at Case Western Reserve University instead. It was there he met his wife Martha, a future elementary school science teacher.

By the time Nester finished his postdoctoral training at Stanford, they were ready for a change of scenery, and he accepted a position with the UW School of Medicine’s Department of Microbiology. “The future looked brightest here,” says Nester. “It was a relatively new medical school with an excellent microbiology department, and I felt that I could do good science here with the collegial support that the UW and the department offered.”

Throughout his career, Nester found a supportive and creative environment that welcomed interdisciplinary collaboration and his curiosity, both of which he nurtured during his years as a professor and department chair.

“Microbiology has a tremendous range of interests,” he says. “There are a lot of cross-disciplinary areas, so you have collaborations with people in biochemistry, genetics and computer science.”

A life-changing collaboration
One such partnership developed into his life’s work: the bacterium Agrobacterium.

It began when Nester’s curiosity turned to crown gall disease — specifically, how Agrobacterium caused the disease. Crown gall is caused by Agrobacterium infecting the plant, but killing the Agrobacterium doesn’t cure the disease.

“After a day or so, you could kill the Agrobacterium, but the disease would continue anyway,” says Nester. “So what is the mechanism by which it causes disease?”

Nester teamed up with biochemist Milt Gordon, PhD, and molecular geneticist Mary-Dell Chilton, PhD ’71. They discovered that Agrobacterium transferred and inserted its own DNA into the plant’s cell, becoming part of the plant’s genome. And, by adding DNA from other organisms to the transferred DNA, researchers could genetically modify the host plant.

It was the first step forward in the genetic engineering of plants. Their discovery would have an enormous impact on the ability to genetically modify plants for decades to come — both in scientific research and at the grocery store.

“The three of us combined had the expertise,” says Nester. “None of us singly could have done it, for sure. In addition, our research program was greatly enhanced by an amazing group of collegial undergraduate, graduate and post-doctoral trainees, most of whom have gone on to successful scientific careers.”

It’s that type of interdisciplinary cross-fertilization, agrees his wife, Martha, that they appreciated so much during his career and that they want to continue to encourage.

That’s why the Nesters decided to make a very special gift to the Department of Microbiology: an endowed professorship. They hope that their newly created endowment will help the department attract and retain top faculty with a commitment to cross-collaboration.

“It’s an outstanding department, and we wanted to help build on the quality that is already here,” says Nester. “Excellent faculty will attract outstanding grad students and postdocs.”

And, of course, excellent collaborations.

As of 3/16/2020, our office operations have moved online. Department Admin staff is available via email/phone and the student advisor (Andrea Pardo) is available via phone or zoom appointment. Please refer to the directory page if you would need a specific person's contact information. 

One concise place for all of your UW related Covid-19 questions including childcare, parking, and research efforts.

Spring quarter will begin with remote instruction on March 30, with fully remote instruction continuing through the end of spring quarter. There will be no in-person classes this spring.

 

Three undergraduate students at the University of Washington are among 396 around the country who have been named Goldwater Scholars for 2020.

The Goldwater Scholarship Program supports undergraduates who “show exceptional promise of becoming this nation’s next generation of research leaders” in science, technology, engineering and mathematics. The scholarships go toward tuition, room and board, fees and books up to $7,500 annually for one or two years.

The 2020 Goldwater Scholars from the UW are Keyan Gootkin, Parker Ruth and Karen Zhang.

Pictures of three students who received Goldwater Scholarships at the University of Washington.

 

Gootkin, Ruth and Zhang.University of Washington

  • Gootkin, who is majoring in astronomy and physics, studies how massive stars end their lives and volunteers with the Theodor Jacobsen Observatory, the League of Astronomers, and the UW’s campus and mobile planetariums.
  • Ruth is pursuing a double major in bioengineering and computer engineering, and studies computational tools to improve health care access. Ruth plans to pursue a doctoral degree in computer science.
  • Zhang, who is studying both microbiology and biochemistry, is interested in “the machineries of life at a molecular level and engineering them to perform novel tasks,” and after graduation would like to obtain a doctoral degree in either bioinformatics or synthetic biology.

The 2020 Goldwater Scholars were selected from a pool of more than 5,000 undergraduate students nominated by 461 academic institutions. A majority of this year’s awardees, 287, are studying the natural sciences, while 59 are majoring in engineering and 50 are majoring in mathematics or computer science. Most say that they intend to pursue a doctoral degree.

The Barry Goldwater Scholarship and Excellence in Education Program was established by Congress in 1986 to honor Barry Goldwater, a five-term senator from Arizona and Air Force Reserve major general. Since 1989, the program has provided 9,047 scholarships totaling more than $71 million dollars.

The University of Washington Population Health Initiative announced the award of approximately $350,000 in COVID-19 rapid response grants to 21 different faculty-led teams. These teams are composed of individuals representing 10 different schools and colleges. Funding was partially matched by additional school, college and departmental funds, bringing the total value of these awards to roughly $820,000.

“A challenge of this magnitude requires us to draw upon the breadth of the university’s expertise to respond, and the range of innovative, collaborative project ideas that were quickly developed for this funding call was both impressive and truly inspiring,” shared Ali H. Mokdad, the university’s chief strategy officer for population health and professor of health metrics sciences. “We believe the 21 projects selected for funding are all well positioned to rapidly accelerate our understanding of, or approach to mitigating, the impacts of this pandemic, which is touching every aspect of our lives.”

The Population Health Initiative COVID-19 rapid response research grants are intended to rapidly accelerate, or jumpstart, novel research designed to better understand or mitigate the impact of COVID-19 on multiple facets of life.

 

Investigators
James I Mullins, Professor, Department of Microbiology
Deborah H. Fuller, Professor, Department of Microbiology
Jesse Erasmus, Postdoctoral Scholar, Department of Microbiology
Jim Fuller, Research Scientist, Department of Microbiology

Project abstract
Nearly all SARS-CoV-2 vaccines efforts are aimed at directing neutralizing antibodies (NAb) towards the viral Spike protein, intended to block the virus from entering cells through its normal receptor. However, these same Spike-directed NAb also have the potential to facilitate viral entry into immune cells through a different receptor, which can lead to Antibody Dependent Enhancement (ADE) of infection and disease. Antibodies from SARS virus infected persons induce ADE in cell culture but it is unclear if this occurs in people. Furthermore, we do not know how much the Spike gene might evolve before possibly returning with new waves of infections. Hence, new Spike vaccines may need to be developed each year the virus returns, as is needed to fight influenza.

We therefore need to rapidly develop alternative vaccines to stop COVID-19 pandemics from current and mutated strains that might circulate in future years. To this end, we designed vaccines to Focus Immune Responses on the Structural inTegrity (FIRST) of SARS-CoV-2 viral proteins. FIRST vaccines are intended to drive T cell and antibody responses that avoid antigenic features of each protein most likely to result in ADE while targeting features unlikely to change rapidly. Here, we will determine the expression of FIRST immunogens in cells and immune responses elicited in mice following delivery as RNA. Subsequently, lead immunogens will be tested with alternative delivery platforms to enable greater stability, lower manufacturing costs and needle free vaccination and a lead formulation selected to take forward into non-human primates and clinical trials.

Monica Cesinger and Brittany Ruhland (both graduate students in the Reniere Lab) have first author papers accepted recently and will be published in the next few weeks. Brittany also had her painting accepted to be on the cover of the journal! According to Dr Reniere, "The watercolor painting by Brittany R. Ruhland represents the interaction between Spx (teal, left) and YjbH (pink, right). We found that the Listeria monocytogenes YjbH protein physically interacts with SpxA1. This watercolor will appear on the cover of the Journal of Bacteriology, vol. 202, no. 12."

Congratulations Monica and Brittany! To see the online publications of these articles, please follow the links below:

Brittany’s paper: https://jb.asm.org/content/early/2020/03/31/JB.00099-20

Monica’s paper: https://onlinelibrary.wiley.com/doi/10.1111/mmi.14508  

Congratulations to our Microbiology Undergraduate Award Winners! We are poud to highlight these talented students and their achievements

Award

Recipient

Message

Photo

Jacques M. Chiller Award

Jessica Porter

I am super grateful to be receiving this award. I am excited to continue pursuing my passion for  microbiology with the freedom from distractions this award has given me, as I go into my senior year. Thank you for this honor!

Don Bassett Award

Haram (Gloria) Kim

Receiving the Don Bassett Award is one of the great honors at UW that I get to earn recognition on all of my dedication to study microbiology since graduating from high school. This acceptance ensures confidence in my future journey on pursuing degrees in medical microbiology/biomedical science and contributing to the related clinical researches!

Dr. Charles A. and Allie Ann Evans Endowed Scholarship

Denise Tong

 

 

David T. Kingsbury Scholarship

Varun Sridhar

My name is Varun Sridhar and I'm a microbiology student and undergraduate researcher in the Dandekar lab. I've looked up to scientists and researchers my whole life, from pioneers like Pasteur and Hooke to my own grandparents, who have always inspired me to stay curious and strive to learn more about the world. I am proud to use these awards to continue their legacy and promote my love for sociomicrobiology and quorum sensing.

Microbiology Undergraduate Research Awards

Pia Andrade

I am grateful for the support that the Mougous lab has provided during my time with them. I plan to use this scholarship for research over the school year and cover costs for my tuition. I will continue to work hard in the lab and pursue my degree in microbiology. Thank you to everyone who helped me get to this point!

Microbiology Undergraduate Research Awards

Santino Iannone

With this award I will be able to spend less time working a part time job and more time being a lab rat

Microbiology Undergraduate Research Awards

Ethan Spencer

I am honored to win the Microbiology Undergraduate Research Award. Being able to doing research at UW has been a big part of my experience at UW, and I have learned so much from it that I would have missed out on from just going to classes. Thankfully, this award will go a long way to helping me make doing research more of a priority for my senior year.

Microbiology Interdisciplinary Award for Research Excellence

Varun Sridhar

My name is Varun Sridhar and I'm a microbiology student and undergraduate researcher in the Dandekar lab. I've looked up to scientists and researchers my whole life, from pioneers like Pasteur and Hooke to my own grandparents, who have always inspired me to stay curious and strive to learn more about the world. I am proud to use these awards to continue their legacy and promote my love for sociomicrobiology and quorum sensing.

Microbiology Education Award

Adrian Bystrom-Cox

 

 

Erling J Ordal Award

Alice Ranjan

 

 

Erling J Ordal Award

Armando Rodriguez

 

 

 

The genome in mitochondria — the cell’s energy-producing organelles — is involved in disease and key biological functions, and the ability to precisely alter this DNA would allow scientists to learn more about the effects of these genes and mutations.  But the precision editing technologies that have revolutionized DNA editing in the cell nucleus have been unable to reach the mitochondrial genome.

Now a team at University of Washington School of Medicine and the Broad Institute of MIT and Harvard has broken this barrier with a new type of molecular editor that can make precise C•G-to-T•A nucleotide changes in mitochondrial DNA. The editor, engineered from a bacterial toxin, enables modeling of disease-associated mitochondrial DNA mutations, opening the door to a better understanding of genetic changes associated with cancer, aging, and more.

The work is described today in Nature. Co-first authors are Marcos de Moraes, a UW postdoctoral fellow in microbiology, and Beverly Mok, a graduate student from the Broad Institute and Harvard University.

The work was jointly supervised by Joseph Mougous, UW professor of microbiology and an investigator at the Howard Hughes Medical Institute (HHMI), and David Liu, professor of chemistry and chemical biology at Harvard University, and HHMI investigator.

“The team has developed a new way of manipulating DNA and used it to precisely edit the human mitochondrial genome for the first time, to our knowledge — providing a solution to a longstanding challenge in molecular biology,” said Liu. “The work is a testament to collaboration in basic and applied research, and may have further applications beyond mitochondrial biology.”

Agent of bacterial warfare

Most current approaches to studying specific variations in mitochondrial DNA involve using patient-derived cells, or a small number of animal models, in which mutations have occurred by chance. “But these methods pose major limitations, and creating new, defined models has been impossible,” said co-author Vamsi Mootha, institute member and co-director of the Metabolism Program at Broad. Mootha is also an HHMI investigator and professor of medicine at Massachusetts General Hospital.

While CRISPR-based technologies can rapidly and precisely edit DNA in the cell nucleus, greatly facilitating model creation for many diseases, these tools haven’t been able to edit mitochondrial DNA because they rely on a guide RNA to target a location in the genome. The mitochondrial membrane allows proteins to enter the organelle, but is not known to have accessible pathways for transporting RNA.

One piece of a potential solution arose when the Mougous lab identified a toxic protein made by the pathogen Burkholderia cenocepacia. This protein can kill other bacteria by directly changing cytosine (C) to uracil (U) in double-stranded DNA.

“What is special about this protein, and what suggested to us that it might have unique editing applications, is its ability to target double-stranded DNA. All previously described deaminases that target DNA work only on the single-stranded form, which limits how they can be used as genome editors,” said Mougous. His team determined the structure and biochemical characteristics of the toxin, called DddA.

“We realized that the properties of this 'bacterial warfare agent' could allow it to be paired with a non-CRISPR-based DNA-targeting system, raising the possibility of making base editors that do not rely on CRISPR or on guide RNAs,” explained Liu. “It could enable us to finally perform precision genome editing in one of the last corners of biology that has remained untouchable by such technology — mitochondrial DNA.”

“Taming the beast”

The team's first major challenge was to eliminate the toxicity of the bacterial agent — what Liu described to Mougous as “taming the beast” — so that it could edit DNA without damaging the cell. The researchers divided the protein into two inactive halves that could edit DNA only when they combined.

The researchers tethered the two halves of the tamed bacterial toxin to TALE DNA-binding proteins, which can locate and bind a target DNA sequence in both the nucleus and mitochondria without the use of a guide RNA. When these pieces bind DNA next to each other, the complex reassembles into its active form, and converts C to U at that location — ultimately resulting in a C•G-to-T•A base edit. The researchers called their tool a DddA-derived cytosine base editor (DdCBE).

The team tested DdCBE on five genes in the mitochondrial genome in human cells and found that DdCBE installed precise base edits in up to 50 percent of the mitochondrial DNA. They focused on the gene ND4, which encodes a subunit of the mitochondrial enzyme complex I, for further characterization. Mootha's lab analyzed the mitochondrial physiology and chemistry of the edited cells and showed that the changes affected mitochondria as intended.

“This is the first time in my career that we’ve been able to engineer a precise edit in mitochondrial DNA,” said Mootha. “It's a quantum leap forward — if we can make targeted mutations, we can develop models to study disease-associated variants, determine what role they actually play in disease, and screen the effects of drugs on the pathways involved.”

Future developments

One goal for the field now will be to develop editors that can precisely make other types of genetic changes in mitochondrial DNA.

“A mitochondrial genome editor has the long-term potential to be developed into a therapeutic to treat mitochondrial-derived diseases, and it has more immediate value as a tool that scientists can use to better model mitochondrial diseases and explore fundamental questions pertaining to mitochondrial biology and genetics,” Mougous said.

The team added that some features of DdCBE, such as its lack of RNA, may also be attractive for other gene-editing applications beyond the mitochondria.

This work was supported in part by the National Institutes of Health (R01AI080609, U01AI142756, RM1HG009490, R35GM122455, R35GM118062, and P30DK089507), Defense Threat Reduction Agency (1-13-1-0014), Merkin Institute of Transformative Technologies in Healthcare, and University of Washington Cystic Fibrosis Foundation.

 

SEATTLE — The new UW Vaccine candidate was created using replicating RNA. Like other vaccines, it triggers the body's immune system to create defenses to COVID-19. But it's the fact that the RNA vaccine reproduces itself inside the body that makes it special.

“What this vaccine does is once it gets in the cell, everything is the same, but then it starts replicating itself, producing more copies of itself. That will produce more vaccine protein and, potentially, make it more immunogenic,” said UW Microbiology professor Deborah Fuller. She is in charge of the laboratory that developed the vaccine.

She says tests and mice and monkeys show that it produces a strong, potentially long -lasting immune response. “We were able to induce very strong immune responses after a single dose, which would be consistent with a vaccine that’s producing much more vaccine antigen.”

Because billions of doses will be needed, a vaccine needs to be easy to make and non-perishable.

Researcher Jesse Erasmus developed a two-part formulation that can go without refrigeration for a week.

Seattle bio-tech firm HDT created the microscopic drops of oil used to transport the RNA vaccine inside human cells.

“So, you can scale up manufacturing of the formulation and scale up manufacturing of the RNA and stockpile each of these things independently. And then you do a simple one-to-one bedside mix prior to vaccination,” Erasmus said.

They're on track to launch the first stage of human trials later this summer. This could be the very first RNA vaccine to go into widespread human use.

“Having worked in nucleic acid vaccines all my life, this is actually what I say is the revolution,” Fuller said.

A study of the findings has been published in Science Translational Medicine. Click here to read more.

 

COVID19 SELF-ATTESTATION: Per Department of Microbiology policy, all personnel entering any UW 
locations are required to submit an online COVID19 self-attestation on the day of entry. 
Self-attestation links are listed below:
1.  For all personnel with Workday Employee Identification (EID):

•     login to Workday

•    Click on the Attestation icon and submit your response:

2.  For personnel without Workday EID: login to CATALYST Self-Attestation Link

REQUIRED TRAINING: School of Medicine COVID19 Safety online training must be completed by all personnel and prior to entering UW location.

Seminars will be held at 10am on Tuesdays via zoom for the forseable future rather than the normal 4pm time. Mark your calnedars!

Dear Microbiology Department,

We are so excited to be sending you the second Diversity Committee newsletter, the first of which to be within the school year. For many of us, continued protests, difficult conversations, and anti-rascist activism have become a much larger part of our daily life than ever before. We hope that this letter can serve our community this fall by channeling the ongoing movement into a fortification of anti-rascist and inclusive practices at the local (can we say Micro?) levels of our labs, department, and university. Furthermore, we would like to use this letter to welcome all those who have newly joined us this year as staff, faculty, post-doctoral fellows, and students! We hope this document  provides a helpful introduction to the resources available at UW and acclimates our new colleagues to UW Microbiology’s efforts towards equity and inclusion in STEM. As always, please reach out to the committee with any questions or comments about the contents of this letter.

-The Diversity Committee 

Can I stop wearing a mask after getting a COVID-19 vaccine?

No. For a couple reasons, masks and social distancing will still be recommended for some time after people are vaccinated.

To start, the first coronavirus vaccines require two shots; Pfizer’s second dose comes three weeks after the first and Moderna’s comes after four weeks. And the effect of vaccinations generally aren’t immediate.

People are expected to get some level of protection within a couple of weeks after the first shot. But full protection may not happen until a couple weeks after the second shot.

It’s also not yet known whether the Pfizer and Moderna vaccines protect people from infection entirely, or just from symptoms. That means vaccinated people might still be able to get infected and pass the virus on, although it would likely be at a much lower rate, said Deborah Fuller, a vaccine expert at the University of Washington.

And even once vaccine supplies start ramping up, getting hundreds of millions shots into people’s arms is expected to take months.

 

Fuller also noted vaccine testing is just starting in children, who won’t be able to get shots until study data indicates they’re safe and effective for them as well.

Moncef Slaoui, head of the U.S. vaccine development effort, has estimated the country could reach herd immunity as early as May, based on the effectiveness of the Pfizer and Moderna vaccines. That’s assuming there are no problems meeting manufacturers’ supply estimates, and enough people step forward to be vaccinated.

The U.S. Food and Drug Administration (FDA) has granted emergency use for two new coronavirus vaccines, one developed by the drug company Pfizer and the biotech company BioNTech and the other by the biotech company ModernaTX. Both are mRNA vaccines and have similar structure.

Both vaccines contain modified mRNA that provides the instructions for the synthesis of the SARS-CoV-2 spike glycoprotein antigen. Its mRNA is enveloped in lipid nanoparticles (LNPs) to prevent degradation and enhance uptake into cells.

The vaccine particles are taken up into cells by endocytosis. The vaccine’s mRNA is then used by the cell’s ribosomes in the cytosol to produce SARS-CoV-2 spike glycoproteins. These proteins then migrate to the cell surface and fragments are presented to the patrolling immune cells by proteins structures called major histocompatibility complexes (MHC).

About the vaccines

Pfizer and BioNTech vaccine

The Pfizer and BioNTech vaccine, called BNT162b2, is given by intramuscular injection in 2 doses, 3 weeks apart.

Results to date suggest the vaccine is highly effective.

In a large, randomized, double-blind, placebo-controlled Phase II/III clinical trial that enrolled >43,000 participants, the vaccine has been found to have an efficacy of 95%, at an interim analysis with a median of 2 months follow up, MMWR reports. (1)

According to the FDA briefing document prepared for the FDA’s Advisory Committee on Immunization Practices (ACIP) meeting, “Consistent high efficacy (≥92%) was observed across age, sex, race, and ethnicity categories and among persons with underlying medical conditions as well as among participants with evidence of previous SARS-CoV-2 infection.” (2)

Results to date suggest the BNT162b2 is safe.

According to the FDA, the frequency of serious adverse events was low (0.5%), without meaningful imbalances between study arms with the exception of more frequent, generally mild to moderate reactogenicity in participants <55 years of age, such as fever, headache and pain at injection site. (2)

“The safety profile of BNT162b2 was generally similar across age groups, genders, ethnic and racial groups participants with or without medical comorbidities, and participants with or without evidence of prior SARS-CoV-2 infection at enrollment.” (2)

ModernaTX vaccine mRNA-1273

On December 18th, the FDA granted emergency use authorization of a second mRNA vaccine, called mRNA-1273, developed by ModernaTX, Inc. The vaccine is administered in 2 doses by intramuscular injection 4 weeks apart.

Results to date suggest mRNA-1273 is effective.

Evidence supporting the authorization is derived primarily from a randomized, double-blind, placebo-controlled Phase III clinical trial that enrolled approximately 30,000 participants. Interim findings, using data from participants with a median of 2 months of follow-up, indicate that the Moderna COVID-19 vaccine efficacy after 2 doses was 94.1%. (3)  “High efficacy (≥86%) was observed across age, sex, race, and ethnicity categories and among persons with underlying medical conditions. (3)

Results to date indicate mRNA-1273 is safe.

According to the FDA: “Local site reactions and systemic solicited events after vaccination were frequent and mostly mild to moderate. The most common solicited adverse reactions were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%); 0.2% to 9.7% were reported as severe, with severe solicited adverse reactions being more frequent after dose 2 than after dose 1 and generally less frequent in adults ≥65 years of age as compared to younger participants.” [4]  There were no anaphylactic or severe hypersensitivity reactions with close temporal relation to the vaccine. (3)

As of December 3, 2020, there were a total of 13 deaths reported in the study (6 vaccine, 7 placebo). These deaths represent events and rates that occur in the general population of individuals in these age groups. The frequency of non-fatal serious adverse events was low and without meaningful imbalances between study arms (1% in the mRNA-1273 group and 1% in the placebo group).” (3)

Q&A with Dr. Deborah Fuller

Dr. Fuller is a vaccinologist and professor of microbiology at the University of Washington.

Q: Can mRNA vaccines like BNT162b2 alter your DNA?

A: Previous research has found that mRNA vaccines do not alter cellular DNA. These vaccines do not include instructions for a viral reverse transcriptase, which would allow the generation of complementary viral DNA that, in theory, could insert into a cell’s genome. Moreover, the vaccine mRNA remains in the cytosol and does not enter the nucleus where genomic DNA is located.

Q: Any chance of a reverse transcriptase making a complementary DNA to incorporate into the genome?

A: No – DNA makes RNA. RNA does not make DNA. It’s a one-way street.

Q: Are these vaccines self-amplifying?

A: Some experimental mRNA vaccines include instructions for a viral replicase that increases production of the viral protein. Such vaccines are called “self-amplifying.” The mRNA used for both the Pfizer and ModernaTX vaccines codes only the viral spike protein and are not self-amplifying.

However, there are 2nd generation mRNA vaccines in development, including one in my lab, that are self-amplifying. To self-amplify, these mRNA vaccines also express another viral protein (replicase) that instructs the mRNA to make multiple copies of itself. Multiple copies of mRNA in the cell can produce more vaccine protein and more vaccine protein can produce stronger immune responses.

Self-amplifying mRNA vaccines are just entering clinical trials now and if they are shown to be efficacious and safe, they could induce stronger immune responses with lower doses resulting in a more cost-effective vaccine.

Q: What is the reactivity to the lipid nanoparticle?  The latest issue of Science cites that this vehicle may be quite reactive, at least in other species where it has been used.  And if it is, does this negate using it as a vehicle for other future vaccines in a person?

A: The lipid nanoparticle serves 3 functions: 1) It stabilizes the mRNA, 2) it helps deliver the mRNA into the cell and 3) it has adjuvant activity that helps amplify the immune responses.

This adjuvant activity works by stimulating an innate immune response, which helps to increase antibody responses against the vaccine antigen (Spike protein) produced by the mRNA vaccine. That innate response is what causes reactogenicity. But it’s not presented to our immune system in a way that we make adaptive immune responses or antibody. As such, repeated use of the lipid-nanoparticle should not result in the induction of adaptive immune responses that will limit repeated use of lipid-nanoparticles with other vaccines or medicines.

This is in contrast to the vaccines being developed by Johnson & Johnson  and Astrazeneca. These vaccines use viral vectors (adenoviruses) to deliver the genetic code that instructs the cell to produce the Spike protein. With these vaccines, we make antibody against both the adenovirus and the Spike protein. The build-up of antibody against the adenovirus with repeated boosting of the vaccine, can, in time, negate potency of these vaccines since the antibody against the virus would block the adenovirus from delivering the mRNA into the cell.

Q: I understand that double-stranded RNAs may form with mRNA vaccines—is this a problem by activating the innate immune system that responds to such structures?  And what effect does this have on the efficacy of the vaccine?

A: Double-stranded (ds) mRNA is a potent pathogen-associated molecular pattern or PAMP that is sensed by multiple cellular pathways and can lead to robust, potentially harmful type I interferon production and increased reactogenicity. Advances in mRNA technology in the last decade have resulted in the development of efficient methods to remove ds mRNA through fast protein liquid chromatography (FPLC) and high performance liquid chromatography (HPLC). In addition, nucleoside modifications incorporated into the mRNA sequences inhibit the ability of the RNA vaccines to form ds mRNA.

Q: What is known about which cell types pick up the mRNA?  Does this matter to the immune response?

A: The mRNA vaccines are injected into the muscle, and we know muscle cells express the vaccine antigen which is then picked up and presented by antigen presenting cells that present the antigen to the B and T cells that help make antibody. Some mRNA can also get into the antigen presenting cells.

Q: There have been reports of Bell’s palsy among the vaccine recipients. Is that a risk?

A: There were four cases of Bell’s palsy in the Pfizer vaccine group compared with no cases in the placebo group.(2)  But the four cases in the vaccine group do not represent a frequency above that expected in the general population. In the ModernaTX, there were three cases in the vaccinated group, one in the placebo group. (5) However, because these cases occurred shortly after vaccination, a link to the vaccine cannot be ruled out. FDA monitoring will continue.

Q: What other vaccines are in the pipeline?  How might they compare to the Moderna product?

A: See above regarding 2nd generation self-amplifying RNA vaccines  and also adenoviruses under development by Johnson & Johnson and Astrazeneca. While adenovirus vaccines have the potential to build pre-existing immunity against the adenovirus and limit their repeated use, they do have a significant advantage in that they are very inexpensive to produce large numbers of doses, they are more stable and, in the case of the Johnson & Johnson vaccine, it may be able to induce protective immunity in a single dose.

The New York Times has been tracking all the vaccines in development with descriptions of the vaccines and where they are in development and testing.

Read the article

Q: If we are going to receive a new type of vaccine where little is known about it, are there investigators at UW Medicine who are interested in studying those vaccinated?

A: Yes – there is a large team of investigators who have been studying convalescent COVID-19 patients and are now preparing to study vaccinated subjects. Major questions to address include: What level of antibody protects? What underlying factors influence the response to these vaccines? How durable is the immunity? And many others.

The National Academy of Sciences will honor 20 individuals with awards in recognition of their extraordinary scientific achievements in a wide range of fields spanning the physical, biological, and medical sciences. Joseph D. Mougous, University of Washington and Howard Hughes Medical Institute, will receive the NAS Award in Molecular Biology for pioneering work in microbiology. The award is presented with a $25,000 prize.

After more than 15 years serving as Vice Provost for Research, Mary Lidstrom will step down from her position at the end of August, with plans to return full time to the faculty, concentrate on her research, and establish mentoring and diversity, equity and inclusion programs. Lidstrom and her team in the Office of Research have made it their mission to support research by supporting researchers, including helping faculty navigate and make sense of the bureaucracy, paperwork and regulations that come along with their jobs.

The Office of Research and Graduate Education presents Microbiology's own Dr Joseph Mougous speaking on "The Big Consequences of Micro-Scale Warfare".  Tune in 11 March 2021 at 12pm.

Though they are by definition single-celled organisms, bacteria can exhibit properties more often ascribed to multicellular life. Our group aims to identify, characterize, and eventually, exploit, pathways that bacteria use for intercellular communication and competition. In this presentation, I will discuss our recent progress toward understanding the diversity of mechanisms by which antibacterial toxins delivered by assorted specialized secretion systems act upon recipient cells. A second focus of the talk will relate to the impact of interbacterial antagonism on microbial communities and bacterial evolution.

 

Our three newest faculty members, Dr Patrick Mitchel, Dr Monica Guo, and Dr Alex Meeske, have officially started at UW. They are seen here in their new lab space at SLU.

Congratulations to Microbiology Undergraduate, Daniel Chen! Daniel has been selected with four other UW students to receive the coveted Goldwater Scholarship

Daniel Chen is double majoring in both Informatics and Microbiology (where he is pursuing departmental honors). He currently conducts research under Dr. Yapeng Su and Professor Jim Heath in the Heath lab at the Institute for Systems biology. His research is focused on utilizing the single-cell multi-omic paradigm to analyze COVID-19 peripheral blood mononuclear cells to identify the disease state effects of SARS-CoV-2 on patient immune systems. Such research has also branched out into investigating heterogenous patient responses to COVID-19 in convalescence along with interrogation of patient epigenomes to identify the early-stage immune cell subpopulations responsible for humoral immunity formation and the epigenomic changes that may guide such. In combination with Chen’s previous research investigating melanoma subpopulations using single-cell transcriptome (scRNA-seq) and epigenome (scATAC-seq) data, his current research projects have continued to push and develop his passion for biomedical informatics particularly when applied to clinically relevant problems.

Chen has previously been awarded the Levinson Emerging Scholars award and the Mary Gates Research Scholarship (for both Winter and Autumn 2020), and is also listed on the Annual Dean’s List. Outside of class and research he enjoys hiking in nature preserves and crocheting amigurumi animals. After his undergraduate studies, Chen intends to pursue an MD-PhD centered on leveraging computational resources and advances to solve human medical challenges such as cancer and infectious diseases. He particularly looks forward to identifying best practices and applications for such research to develop more accessible medical solutions for the given problem.

Daniel’s near-term and long-term goals: I plan on initially earning an MD-PhD in either Bioinformatics or Bioengineering. Then I hope to pursue a faculty position at a university to conduct translational research in biomedical-informatic oriented fields.

Daniel’s tips for future applicants: Reach out to the OMSFA staff members because they do an amazing job in providing advice and resources on the application. Definitely take advice with a grain of salt and speak to what personally drives you which may require some time to just sit-down and really dig deep into what is the unique, personal reason your pursuing your current goals, what are they and what do they lead to (i.e. what are your future goals; why is what you’re doing now helping your career).

"Fuller studied biology, Spanish and mathematics at Hope. In 2001, she received a Doctorate of Philosophy in Molecular and Cellular Pathology at the University of Wisconsin.

She joined the faculty at Albany Medical College in New York as an associate professor in the Center for Immunology and Microbial Disease in June 2007 following three years as an assistant professor at the University of Pittsburgh in the Department of Molecular Genetics and Biochemistry. Prior to her academic career, she was a senior scientist at PowderJect Vaccines in Madison, Wisconsin, where she co-invented nucleic acid vaccine strategies that she still employs for her academic research. She has been at the University of Washington since 2010. 

Fuller has published 90 manuscripts and book chapters and is a co-inventor on over a dozen patents on the subjects of viral immunity, antivirals and DNA and RNA vaccines. She has received multiple grant awards from the National Institutes of Health and nonprofit foundations to fund her research, and she serves on several national scientific committees and advisory boards. In 2017, she co-founded Orlance, Inc., a biotechnology company developing next generation needle-free vaccine delivery technologies for DNA and RNA vaccines.

In the past year, Fuller played a key role in advancing vaccines and antivirals for COVID-19. Her lab had developed second-generation DNA and RNA vaccines for SARS-CoV-2 including one that is scheduled for human clinical trials in Spring 2021 to enable rapid manufacture and more accelerated worldwide distribution. At the start of the pandemic, Fuller was appointed to the Leadership Team on the National Institute of Health’s COVID-19 Vaccines and Therapeutic Evaluation Network that aims to accelerate the most promising vaccines and antivirals to clinical testing. In the last year, she has also served a major role in enhancing public understanding of the science behind the COVID-19 vaccines. She has been a regular guest expert on Bloomberg TV, CNN, NPR and local Seattle area news and has contributed to multiple articles published by the Washington Post, The Associated Press, The Wall Street Journal, Vox, conversation.com and others.

As a student at Hope, she participated in varsity women’s track, cross country and swimming, the Mortar Board honor society, and an off-campus study semester in Spain. As an alumna, she serves as part of the college’s Career Resource Network.

Fuller lives in Bainbridge Island, Washington. She shares two sons with her husband, Jim Fuller."