“When a mass vaccination campaign is rolled out, adverse events are observed more acutely and more accurately than during the slow trickle that goes with any other kind of vaccine or drug distribution. The infrequent becomes more frequent because the number of people vaccinated in a very short time is so large — a one-in-a-million problem becomes one per day rather than one every two to six months,” writes the 91̽��’s  in a recent , jointly produced by Johns Hopkins University and the UW.

The key to catching adverse effects is an effective surveillance system, which worked in the blood-clotting case and must continue to be supported with time, energy and resources.

“The advantage we have at this point is that we know how to diagnose and treat it, so there’s at least a potential to lessen the impact of the disease,” Corey wrote in . “A thorough review of the risk benefit of the vaccines was performed by both the CDC and the FDA and both of these organizations advised that people should be alerted about the possibility of (blood clotting) and to seek medical evaluation if they experience prolonged abdominal pain, worsening headache, or shortness of breath in the days following vaccination.”

This should improve public confidence that these vaccines, including the Johnson & Johnson vaccine which was put back into circulation, are still being monitored for effectiveness and safety. And, Corey points out, while adverse effects will be investigated and vaccines evaluated in light of them, the risk-to-benefit ratio of the vaccines needs to be kept in perspective. After all, the odds of being hit by a car are about one in 4,292 and dying as a result are about one in 47,273.

“Clinical trials have given us a wealth of information about the efficacy and safety profile of vaccines for COVID-19. But the work of gathering evidence and weighing results in the context of an ongoing pandemic isn’t done,” said Corey.

To read this and other articles by Corey and other experts, visit the  blog series created by Johns Hopkins and the 91̽��as an outcome of the joint symposium — Preserving the Scientific Integrity of Getting to COVID-19 Vaccines: From Clinical Trials to Public Allocation — the two universities hosted in October.

Dr. Larry Corey is the leader of the  (CoVPN ) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID 19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at 91̽�� and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

With COVID-19 cases again in many parts of the country — including Washington state where were pushed back to Phase 2 effective Friday — there’s a growing between continuing to give both doses of Moderna or Pfizer-BioNTech vaccines close together, or giving them months apart in order to get first shots in more shoulders faster.

The argument for giving more people the first dose before circling back months later to give the second, which provides the strongest protection against COVID-19, centers on the numbers: It’s better, the argument goes, for more people to be partially protected in order to curb infections by the coronavirus than to have fewer people fully vaccinated. Advocates of this hope partial vaccinations would not only curb infections but also save lives, since a single dose significant protection against illness.

Under the current strategy, the second dose of either two-dose vaccines comes within a few weeks of the first shot. The dose-sparing strategy, considered either because a community has too few doses or climbing infections, schedules the second dose for months later.

However, the dose-sparing strategy could create even greater trouble than we’re currently facing, argues the 91̽��’s  in a recent  jointly produced by Johns Hopkins University and the UW.

“I say that because the viruses we’re going to encounter today and what we will encounter in the next several months are not the same viruses that we tested the vaccines on and upon which the single-dose [strategy] data are based; they are going to be more formidable adversaries,” writes Corey, a professor of medicine and virology at the 91̽��School of Medicine.

These future versions of the viruses are “escape variants” that have evolved in the environment of weak immune responses — the body in this case has produced a strong enough immune response to tamp down the infection but not strong enough to keep mutated viruses from spreading.

“How do we overcome escape variants? We do so by using the full strength of the tools we have available to us. We provide immunity that is capable of eliminating the virus quickly and we don’t expose the virus to lots of people with low levels of immunity,” Corey writes.

Corey adds that the coronavirus variants currently spreading require a stronger immune response to beat, and current versions of the two-dose vaccines were designed to battle the original versions of the virus. So, using one dose to create partial immunity to a variant that requires a stronger immune response to beat could create an environment for new, tougher variants to evolve and spread. However, giving the second dose creates a much stronger immune response and can stop escape variants.

“While my musings are inferential, I feel we will actually do more harm than good by markedly increasing the population of people with partial protective immunity,” Corey writes.

To read this and other articles by Corey and other experts, visit the  blog series created by Johns Hopkins and the 91̽��as an outcome of the joint symposium — Preserving the Scientific Integrity of Getting to COVID-19 Vaccines: From Clinical Trials to Public Allocation — the two universities hosted in October.

Dr. Larry Corey is the leader of the (CoVPN ) Operations Center, which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic and the Chair of the ACTIV COVID 19 Vaccine Clinical Trials Working Group. He is a Professor of Medicine and Virology at 91̽�� and a Professor in the Vaccine and Infectious Disease Division and past President and Director of Fred Hutchinson Cancer Research Center.

While development of vaccines now being distributed to combat COVID-19, the deadly disease caused by the novel coronavirus, are a “remarkable achievement” that demonstrate the power of science to save lives, mistrust and fear continue to cause nearly to say they would be unlikely to get vaccinated.

Some of that mistrust stems from before the pandemic, but unfortunate politicization of COVID-19 vaccine development is also to blame. When the current administration jumped in to claim credit for the rapid development of the vaccines, that act personalized the science behind its creation.

“By personalizing it, it became politicized. It created an odd discord, as if science – and what is in a vial – had something to do with whether you’re a Republican or Democrat,” writes Corey.

Also, the administration put an enormous amount of funding into the rapid development of vaccines, but then named the effort Operation Warp Speed. And, says Corey, speed in medical scientific development “is not something we associate with positive outcomes.”

So, given the historic mistrust of vaccinations, the politicization of COVID-19 vaccines and an unfortunate project name, vaccine hesitancy is understandable. And yet the pandemic rages on. How, then, to bridge the divide between jubilation at the production of incredibly successful vaccines and mistrust?

“It will take work by all of us – in the scientific community and in the broader public. It will take hard work to convey the importance of vaccination. It will take time to rebuild trust across the divide. And it will take a public open to healing discourse; a public who remains curious and eager to know more as we learn more. Because we will,” Corey writes.

To read this and other articles by Corey and other experts, visit the  blog series created by Johns Hopkins and the 91̽��as an outcome of the joint symposium —  — the two universities hosted in October.

Dr. Larry Corey is an internationally renowned expert in virology, immunology and vaccine development and a leader of the  (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a professor of medicine and virology at 91̽��School of Medicine and a professor in the Vaccine and Infectious Disease Division and past president and director of Fred Hutchinson Cancer Research Center.

Answering questions around how vaccines affect transmission of the virus is “of obvious importance” and research will be conducted once people begin getting vaccinated, Corey writes in a new jointly produced by Johns Hopkins University and the UW. But we all must still wear masks, physically distance, wash our hands frequently, and avoid large gatherings — even when most people have been vaccinated.

“If vaccinated individuals are capable of transmitting infection,” Corey writes, “then anybody who is not vaccinated fares no differently before than after the introduction of a COVID-19 vaccine. With vaccine hesitancy resulting in fewer people agreeing to be vaccinated, we do not yet know whether and when we will be able to markedly reduce the public health implications of COVID-19 and reduce its circulation in the workplace, in close communities and stop super-spreading events.”

In addition, Corey notes that mathematical models suggest that vaccines could create a situation in which many more people carry the virus without showing symptoms, become more cavalier about whether they can spread the virus and therefore unknowingly infect even more people.

“This realization helps explain why we must optimize coverage and overcome vaccine hesitancy, especially in persons who are at high risk,” Corey writes.

To read this and other articles by Corey and other experts, visit the blog series created by Johns Hopkins and the 91̽�� as an outcome of the joint symposium — — the two universities hosted in October.

Dr. Larry Corey is an internationally renowned expert in virology, immunology and vaccine development and a leader of the (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health to respond to the global pandemic. He is a professor of medicine and virology at 91̽��School of Medicine and a professor in the Vaccine and Infectious Disease Division and past president and director of Fred Hutchinson Cancer Research Center.

When a vaccine to fight COVID-19 has been approved by the FDA for distribution, it’s unlikely that at first there will be enough doses for everyone. Consequently, the United States will need an equitable and effective plan for who gets those first doses, how they get them and who’s next.

Just as important, that plan — like the vaccine itself — has to be trusted and accepted by the general public.

To accomplish this complicated and potentially fraught task, the CDC , which guides the CDC’s distribution of FDA-authorized vaccines, has been holding public meetings and gathering scientific evidence.

On Thursday, the committee published a explaining the scientific and ethical principles guiding the development of the recommendations it will make to the CDC. The Viewpoint article also sets out several recommendations the Advisory Committee is considering for those first days, when vaccine supplies will be limited.

, lead author of the Viewpoint and a clinical professor of global health in the 91̽��School of Public Health, said: “An important objective of the JAMA article is to help inspire public confidence. We are a group of outside experts, committed to making decisions based on the best available scientific evidence in a clear and transparent way. We want people to understand the process.”

The recommendations the committee is considering address that early window when there are not enough doses to go around. Based on available data, the committee writes: “There is a clear consensus” that initial doses should be used to vaccinate health care personnel. However, Bell emphasized, recommendations will not be made until a vaccine is authorized or licensed by the FDA and the advisory committee has conducted an independent review of data from phase III clinical trials.

Health care personnel means the 20 million people who work in hospitals, long-term care and assisted living facilities, and the staff of home health care facilities, outpatient clinics, pharmacies and emergency medical services. These workers have the highest potential for direct or indirect exposure to patients or infectious materials, the article states.

The committee is considering a number of other groups for the next step of this first phase. These include essential workers: 60 million people who work in food production and distribution, education, law enforcement and other jobs that support critical infrastructure. Also in this “Phase 1b” population could be the roughly 100 million adults with one or more high-risk medical conditions (for example obesity, diabetes or cardiovascular disease) and 53 million adults ages 65 and older, including the 3 million living in long-term care facilities.

“We are very aware of the strong evidence that certain disadvantaged populations have been disproportionately affected by the pandemic. And we are determined to do everything we can to make sure that those populations have fair and equitable access to the vaccine,” said Bell, who is a voting member of the committee.

“If we assume for the moment that the FDA has authorized or licensed a number of vaccines which are safe and effective, then one of the biggest challenges is going be the complexity of the distribution process. Recognizing this, we have been considering feasibility and implementation issues in our decision-making process. But I think probably one of the greatest, if not the greatest, challenge is going to be inspiring people to have confidence in the process, in the fairness, in the transparency — and to trust that it’s a good idea to get vaccinated,” said Bell.

Bell and the other 14 of the Advisory Committee on Immunization Practices hope the ethics driving their process and their focus on vaccine safety will inspire that trust.

“We always put safety first. We are watching the clinical trials very closely and evaluating safety, as is the FDA and their advisory committee. And we will be continuing to look closely at the safety of the vaccines as we go forward,” Bell said.

Co-authors include Dr. José Romero, University of Arkansas and Arkansas Department of Health, Little Rock; and Dr. Grace Lee, Stanford University School of Medicine. The article reflects the opinion of the entire committee.

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To arrange interviews with Dr. Bell, contact Jake Ellison at Jbe3@uw.edu.

Dr. Anna Wald, 91̽�� professor of medicine and laboratory medicine in the School of Medicine and professor of epidemiology in the School of Public Health, is among those leading clinical studies of GEN-003. The trials are also taking place at six other centers in the United States.

One of several components of the vaccine was designed at the 91̽��in Dr. David Koelle’s lab in the Division of Allergy and Infectious Diseases, Department of Medicine. Genocea, located near Boston, is a clinical-stage biopharmaceutical company for the discovery and development of T cell vaccines to prevent and treat infectious diseases.

T cells, a type of white blood cells, generate immune responses to pathogens and are important in controlling infections. T cell vaccine research is trying to find safe, effective ways to spur this protective reaction.

Wald and her team presented the initial findings of the first-in-human clinical trial of the novel GEN-003 T cell vaccine Sept. 12 at a session of the Interscience Conference on Antimicrobials Agents and Chemotherapy in Denver.

The team reported results from the Phase 1/2A clinical study. The ongoing Phase 1/2A clinical trial of GEN-0300 is a double-blind, placebo controlled, dose escalation study to evaluate safety and measure the immune response generated by the candidate vaccine.  The study enrolled 143 volunteers with moderate-to-severe recurrent genital herpes.

Genocea plans to move into Phase 2 of this trial in 2014 to further evaluate GEN 003’s safety and effectiveness in a larger group of patients.

Genital herpes is a sexually transmitted disease caused by herpes simplex virus type 2. The infection can provoke recurring episodes of painful genital sores.  An estimated 50 million to 60 million Americans are affected. At present, no vaccine is approved to prevent or treat genital herpes.

At unpredictable times in those carrying the infection, the herpes virus will come out of hiding and  surface on the genitals, sometimes producing blisters and discomfort, and sometimes arising without any noticeable symptoms.  This surfacing is called viral shedding. Shedding can spread the infection to others during sexual relations or during birth. Viral shedding is a marker both of the risk of recurrence and the transmission of infection.

Data from planned analysis of the Phase 1/2a clinical study showed that patients who received three doses of GEN-003 had reductions in the frequency of viral shedding of up to 51 percent. The vaccine is administered through an arm muscle injection. Patients who received a placebo had no decline in viral shedding.

The results also demonstrated that immunization with GEN-003 is associated with activation of T cell immunity. In those receiving the vaccine candidate, T cell immune responses increased more than 20 times to one vaccine antigen and more than 10 times to another antigen.  The vaccine candidate also increased neutralizing antibodies to the herpes simplex 2 by five times greater than baseline amounts. The vaccine candidate was, overall, well tolerated by patients.

“These are the first data that provide compelling evidence that a vaccine administered to people with genital herpes can affect their infection,” Wald said. “We are excited that GEN-003 reduced viral shedding as this finding paves the way for future trials that will measure the impact on clinical outbreaks. The ability to reduce viral shedding is critical, as that is the main driver of transmission of HSV-2 to sexual partners and newborns.”

The first-in-human clinical trial was not designed to test whether GEN-003 lessens symptoms or lowers how often a breakout occurs. However, an exploratory analysis suggested that the interval between the first immunization with GEN-003 and the next recurrence of genital herpes might be longer in those receiving the actual candidate vaccine, rather than the placebo injection.

“The initial results are unprecedented in the clinical development of vaccines for herpes simplex virus-2,” noted Chip Clark, president and CEO of Genocea.  “We are proud to be pioneers in the field of T cell-directed vaccines. We will complete this study and continue clinical development of GEN-003 with urgency, in order to bring this promising treatment to a large patient population that is in dire need of an approved vaccine that can prevent or treat their disease. “

Genocea developed the proprietary platform ATLAS, which can identify protective T cell antigens in people exposed to a pathogen. ATLAS mimics the human immune response. ATLAS was instrumental in developing GEN-003.

The vaccine contains, among other components, a proprietary adjuvant, trademarked Matrix-M. licensed from Novavax, Inc. The adjuvant has a product that, in previous clinical studies, has been shown to stimulate B and T cell immune responses.

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Note: Dr. Wald is enrolling women infected with herpes simplex virus 2 in a study to see whether the drug tenofovir, given orally or as a vaginal gel, reduces genital shedding of the virus. Reducing the frequency of viral shedding is the first step to showing that a drug can reduce outbreaks or, potentially, sexual transmission to partners. Tenofovir has been shown in some studies to reduce the risk of acquiring HIV, and in some studies there was also a reduction in the frequency of HSV-2 acquisition, but this is the first time that it is being tested as a drug specifically for HSV-2. To learn more about the study, visit the .

The National Institute of Allergy and Infectious Diseases of the National Institutes of Health has announced the award of a five-year, nearly $15 million contract, including the exercise of all options, to the 91̽��for the Nonhuman Primate Core Functional Genomics Laboratory for AIDS Vaccine Research and Development.

The lab will apply leading-edge biotechnology, biocomputing tools and systems biology approaches to conduct this service. It is anticipated to make inventive improvements in vaccine services and assays.

The principal investigator is Dr. Michael Katze, a 91̽��professor of microbiology who pioneered systems biology to understanding immune responses to infections. He and his colleagues examine the network of responses and interactions between pathogens and their hosts, as well as the factors that influence the dynamics of this struggle.

“The AIDS vaccine field is in need of new approaches. The methods we use allow us to understand the gene expression changes that correlate with vaccine efficacy and will help to design better vaccines,” Katze said.

Their laboratory will receive specimens obtained from ongoing and new high-priority preclinical non-human primate studies conducted in the National Institute of Allergy and Infectious Diseases Division of AIDS Simian Vaccine Evaluation Units and other Division of AIDS -supported preclinical non-human primate studies across the country.  It will become the fourth Simian Vaccine Evaluation Units Core Lab in this effort to end the AIDS epidemic. The existing Simian Vaccine Evaluation Units Core Labs, located at other institutions, cover other aspects of AIDS vaccine preclinical research in non-human primates:  the Humoral Immunology Core Lab, the Cellular Immunology Core Lab, and the Viral RNA Core Lab.

The new 91̽��Non-Human Primate Core Functional Genomics Lab will test specimens to generate specific genomic expression profiles using approaches developed by 91̽��microbiologist Dr. Robert Palermo and other 91̽��research scientists. These profiles are a time-record of gene activity, and rapidly examine many genes at once. The profile reveals those segments of the organism’s genome that are being dynamically utilized. The transcription of information coded in the DNA is the first step in producing a protein to carry out a biological function.

After measuring how experimental conditions alter which genes are turned on or off, a systems-level view is derived. This analysis uses sophisticated mathematical techniques, interaction networks, and computer modeling.  In this approach, other types of data from the vaccine studies are integrated with the genomic expression profiles to find potential predictive signatures. The list of RNA molecules discovered during such characterizations offer clues to the events taking place inside and around living cells.

In evaluating potential AIDS vaccines, data analyzed in this way may point to gene signatures that suggest how much protection a vaccine is expected to provide against HIV. Checking for and measuring gene signatures after vaccination and virus exposure could in part explain a vaccine’s effectiveness in preventing or controlling an infection by illuminating the details of the immune mechanisms evoked by the vaccine.

Palermo commented:  “The vision of the Division of AIDS at the National Institute of Allergy and Infectious Diseases in establishing this Core is very exciting.  The work will inform not only the efforts of individual investigators, but will result in a compendium of such data across many studies and conditions. This will enable sophisticated computational approaches that are dependent on having very large amounts of data, and ideally will lead to insights not accessible with the results of a single study.”

The activities of the 91̽��Non-human Primate Core Functional Genomics Lab will contribute to the many National Institute of Allergy and Infectious Diseases-funded efforts that target discovering effective preventive vaccines against AIDS.  National Institute of Allergy and Infectious Diseases supports testing a variety of candidate AIDS vaccines, and is exploring ways to optimize their ability to elicit immune responses that will prevent infection or control virus replication.

The National Institutes of Health contract number for the 91̽��Core Functional Genomics Lab is HHSN272201300010C.

In June 2011 Dr. Alisa Hideg was a 42-year-old mother and family physician in the prime of her career practicing at Group Health in Spokane when she was diagnosed with estrogen and progesterone receptor negative/HER 2 positive breast cancer.

Breast cancer in young, premenopausal women is usually aggressive. So even after chemotherapy, a double mastectomy, and radiation, with her cancer in remission, Hideg wasn’t ready to take it easy. Both the type of breast cancer and the fact that it happened at a young age made her chances of relapse higher. This knowledge led her to experimental trials, and to the UW’s Tumor Vaccine Group.

Hideg found the 91̽��Tumor Vaccine Group on the National Institutes of Health clinical trials website, ClinicalTrials.gov. She had heard about a trial at the University of Pennsylvania’s Perelmen School of Medicine, where the use of gene-transfer therapy converted the patients’ own immune cells into weapons aimed at cancerous tumors. All 12 patients had advanced stage leukemia; nine of the 12 responded positively to the treatment, and two of the first three patients treated have been in remission for two full years.  The Perlelmen results encouraged her to seek out a 91̽��study to see if she qualified.

The 91̽��Tumor Vaccine Group currently offers clinical trials for patients with breast, ovarian or colon cancer. Hideg is in a very desirable , and being approved to participate wasn’t easy. The goal of the clinical trial is to allow the patient to make and keep enough antibodies to quash any future HER-2 expressing breast cancer.

Dr. Nora Disis, 91̽��professor of medicine and principal investigator of the study, explains how the vaccine may work.

“The vaccine is designed to stimulate a particular cell of the immune system, the T cell, to recognize the HER2 protein (that causes cancer),” Disis said. “If effective immunity is generated, the T cell activated by the vaccine should be able to hunt out tumor cells wherever they may be and destroy them.  This particular study is testing the use of an immune stimulator, ampligen, which may be able to activate the T cells more effectively than other agents we have used before.“

Last month, Hideg received a vaccine dose at 91̽��Medical Center. The process is gentle — a series of four small injections that make a little grid of dots on the upper arm — but the body’s response can be angry. Hideg experienced flu-like symptoms after the first visit. The reaction  may actually be a promising sign that her body is responding to the vaccine.

She’s positive and funny in the face of serious medicine. She tweets pictures of her experience to a network of fans and writes about her cancer in Spokane’s daily newspaper, the Spokesman-Review. In addition to being a doctor, patient and full-time mother, Hideg recently went through a series of intense interviews to add “teacher” to her resume. She has become a clinical faculty member to teach second-year 91̽��medical students at the Spokane WWAMI site.  WWAMI is a regionalized medical education program that covers Washington, Wyoming, Alaska, Montana and Idaho.

“Teaching has always been a part of my clinical practice,” Hideg said. “I have taught medical students, residents and others in my clinic since I finished my own training. This experience has reminded me how important teaching can be and how much I enjoy passing on what I have learned as a physician, a parent, and as a patient. Whether the vaccine is effective for me or not, I am grateful for the opportunity to participate in the trial and help move the science forward. I believe in the potential of vaccine therapy for cancer and perhaps for other diseases also and I want a future with more options for my daughter and for others.”

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The LEED rating notes the design, construction and operation of modern, green buildings. Rating categories include sustainability, water and energy efficiency, materials used, indoor environmental quality and the design process.

Seven floors tall, Poplar Hall hosts about 270 students in studio apartments and double rooms. Its third floor is home to a sustainability community dedicated to social equity and minimal environmental impact.

Molecular engineering and science focus of new UWTV-produced documentary

A half-hour documentary titled “” airs on UWTV, which produced it, Saturday, Sept. 29 at 5:30 p.m. The film focuses on research happening in the UW’s newly opened .

The film takes viewers on a tour of the building and interviews 91̽��faculty working in two focus areas: clean tech and biotech. Dean describes the emerging field of molecular engineering, and talks about the role of the UW’s . Other 91̽��faculty who appear in the program include on nanotechnology to make paintable solar cells, on inexpensive, plastic solar cells, on new solar-powered batteries, on emerging tools and trends in solar technology, on nanotechnology manufacturing, on drug delivery, and on designing new proteins to solve 21^st-century challenges. Steve Pool, a 91̽��alumnus and KOMO television weather anchor, is the host.

The documentary will air regularly through fall and winter on UWTV, and can be seen anytime .

Next flu shot clinic Oct. 15 at 91̽��Tower
91̽��Benefits conducted its first flu shot clinic last week and has several more scheduled through Nov. 1.

Flu shots are free for faculty, staff and retirees covered by a Public Employee Benefits Board health plan and for students covered through the Graduate Appointee Insurance Program or the Student Health Insurance Plan. Be sure to bring your health insurance card – otherwise you must pay $30 and seek reimbursement from your health plan – plus a photo ID and a completed copy of the .

The UWellness says everyone is encouraged to get a flu shot because it’s the single best way to keep from getting and spreading the flu, according to the Centers for Disease Control and Prevention.

91̽��employees and students also can get flu shots through the Hall Health .