January 2020
The UMB Post[doc]
January 2021
Mutant Coronavirus - Is the Vaccine Still Effective?
SPOTLIGHT ON: Colin Brinkman, PhD
Chat with an Expert: Matthew Laurens, PhD
January and February Career Development Events
Introduction
Dear Readers,
Welcome to 2021! The big questions on everyone’s mind: what does the year hold in store for us? It is hard not to wonder whether this year will facilitate some return to normalcy as COVID-19 vaccines are distributed. How will the transfer of power within the executive branch and legislature affect us following a tumultuous year in 2020?
One exciting development is the creation of COVID-19 vaccines! Fittingly, this month, we discuss the deployment of the COVID-19 vaccines with an industry expert, and we talk about new strains of COVID-19 and what this may mean for the future. We also ask a science policy expert and former UMB postdoc how you can get directly involved in science in government and public policy work.
If you would like to be involved in the making of the newsletter and shaping the content we share in 2021, please reach out to us at umbpostdoc@som.umaryland.edu.
We wish you a wonderful start to your year!
Best,
The UMB Post[doc]
Mutant Coronavirus - Is the Vaccine Still Effective?
Long Jiang
SARS-CoV-2 is an RNA (ribonucleic acid) virus that has RNA as its genetic material. Because viral RNA polymerases don’t have the proofreading ability of DNA polymerases, the RNA viruses have very high mutation rates than DNA viruses. In general, some mutants are neutral mutations which means they have no effect on viruses themselves. However, sometimes there are beneficial mutations which can make viruses “live” for longer. Recently, three SARS-CoV-2 variants were added to this “beneficial mutation” category, which is more capable of transmission among people.
New Emergent SARS-CoV-2 Lineages
- A new variant strain of SARS-CoV-2 (B.1.1.7) has been reported in early December 2020 in the United Kingdom (UK). The earliest sampled genomes showed it has occurred in September 2020. The B.1.1.7 lineage has now been designated Variant of Concern (VOC) 202012/01 by Public Health England (PHE). This variant has since been detected in 22 countries around the world, including the United States (US).1
- On December 23, the UK government found another variant of SARS-CoV-2 (501Y.V2 or B.1.351) emerged independently of VOC 202012/01. The study found that this variant has higher infection rates among new cases in South Africa.
- On December 24, the African Centers for Disease Control and Prevention announced that a third variant of the new variant had appeared in Nigeria. Nigeria is the most populous country in Africa, and its confirmed cases of new COVID-19 have increased by 52 percent in the past month. This strain has similarities with the two strains in the UK and South Africa, but these similarities may have evolved independently.
Mutations in Coronavirus: What Has "Changed"?
The surface of the new coronavirus has spike protein (S protein). Human cells express the TMPRSS2 enzyme which can "cut" the S protein, revealing a protein that can bind to the ACE2 receptor on the surface of human cells. After successfully binding to the ACE2 receptor, the new coronavirus can enter human cells. Therefore, any changes in the sequence of the S protein have the potential to contribute to the spread of the virus.2
- The first mutation of the COVID-19 that caused widespread concern emerged many months ago. This mutation was named "D614G" because it mutated the 614th amino acid aspartic acid (D) on the S protein of the coronavirus to glycine (G). Researchers stated that the mutation makes it easier for the coronavirus to enter human cells and greatly increases the transmission rate of the new coronavirus.3
- Among the B.1.1.7 and B1.351 strains that appeared in the UK and South Africa, both of their mutations appeared on the S protein. The viral protein sequence that binds to the receptor is called the "receptor-binding domain" (RBD); the amino acid sequence of RBD determines the efficiency of virus-invading cells. These two new strains both showed an N501Y mutation, in which the 501st amino acid on the S protein was replaced from asparagine (N) to tyrosine (Y). The N501Y mutation can increase the affinity of RBD and ACE2 receptors, which makes it easier for the new coronavirus to infect human cells. This may be the reason why B.1.1.7 showed abnormally high levels in the respiratory tract of patients with new pneumonia.4
- The strain reported in Nigeria has a P681H mutation on the S protein, and this mutation also exists in B.1.1.7. The P681H mutation replaces a proline (P) on the S protein with histidine (H), and the replacement site is just at the position where the TMPRSS2 enzyme "cuts" the S protein. Therefore, it also has the potential to improve the infectivity of the virus.5 However, due to the limited data available, scientists are still unable to make reliable inferences.
- The British B.1.1.7 strain also contains a deletion mutation Δ69-70 in the N-Terminal Domain (NTD). According to ARTIC Network's report, the mutation appeared in mid-July and in the new coronavirus strain that later infected Danish mink. They also showed that the deletion mutation allows the virus to escape the neutralization effect of some monoclonal antibodies, so it may affect the effectiveness of antibodies and vaccines, but its specific impact remains to be analyzed.6
Fortunately, although the mutations in the three strains may make it easier for the virus to invade human cells, there is no evidence that new strains will increase the severity of the disease compared with the older one right now. But it is still needing more studies to confirm.
Does the Mutated Coronavirus Influence the Effect of the Vaccines?
The mRNA vaccines produced by Pfizer/BioNTech and Moderna recognize the S protein of the coronavirus. Therefore, under ideal circumstances, the immune response will produce antibodies against the S protein to neutralize the new coronavirus invading the human body.
However, the new strains all have variations in the S protein of the virus. The question is whether this impacts the efficacy of the vaccine.
To see if the vaccines work against the new strains, both Pfizer and Moderna are testing their vaccines. However, it seemed both companies have confidence about their vaccines.
Uğur Şahin, the CEO of BioNTech, stated that "the sequence of new strain is 99 percent identical to the previous strain," and the vaccine should be able to effectively resist the emerging mutation strains. British Health Secretary Matt Hancock also pointed out that the current vaccines target multiple sites on the S protein of the virus, so a small number of mutations are "very, very unlikely to allow the virus to produce immune escape."7
The Moderna statement also said, "Based on current data, we expect that the Moderna vaccine-induced immunity would be protective against the variants recently described in the UK."8
So far, it is not clear whether the vaccines offer protection against new mutation strains. Although the production of vaccines is very complicated, we should remain optimistic.9 Just like the flu, COVID-19 will be overcome by us sooner or later.
References:
- https://cov-lineages.org/global_report.html.
- Bratosiewicz-Wasik J, Wasik TJ. Does virus-receptor interplay influence human coronaviruses infection outcome? Med Sci Monit. 2020; 26: e928572-1–e928572-10.
- Plante JA, Liu Y, Liu J, Xia H, Johnson BA, Lokugamage KG, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature. 2020 Oct 26. doi: 10.1038/s41586-020-2895-3. Online ahead of print.
- https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563.
- https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567
- https://www.biorxiv.org/content/10.1101/2020.12.14.422555v1.full.pdf
- https://www.fiercepharma.com/pharma/pfizer-moderna-urge-calm-as-they-launch-tests-vaccines-against-mutated-covid-19
- https://khn.org/morning-breakout/will-approved-vaccines-protect-against-new-coronavirus-mutation/
- https://www.nature.com/articles/s41577-020-00480-0
SPOTLIGHT ON: Colin Brinkman, PhD
Shannon Cole
This month, we interviewed Dr. Colin Brinkman, a Program Manager at the US Department of State, where he directs science development projects related to ocean policy. Dr. Brinkman was an AAAS Science and Technology Policy Fellow and an AAI Fellow while at UMB. Here, Colin shares his perspectives on moving from academia to science policy work, life in the world of science policy, fellowship opportunities, and suggestions on getting involved in policy work.
Q: Can you tell us about your career path and your current role? How did you transition from academia to policy?
CB: In 2016, I started as an Association for the Advancement of Science (AAAS) Science & Technology Policy fellowship at the US Department of State, which is where I am now.
I had been becoming interested in policy for a while…I had been involved in some things at UMB that exposed me to some other options. I applied to the American Association of Immunologists (AAI) public policy fellowship, which was a one-year virtual fellowship where you stay at your current postdoc. It involved semi-weekly sessions with a policy team, helping to draft yearly congressional testimony in support of increased NIH funding, going on congressional visits to pitch support for robust NIH budgets to members of Congress, and that was really interesting. I had also done some community outreach work, doing science demonstrations with middle schools. I also worked to found the UMB postdoctoral association, as well as worked with the National Postdoctoral Association. I was involved in notions of policy for science and science policy as well. I was coming to understand that there was a whole universe of opportunities that are still technical in nature and allow you to use many of the skills you acquire with a science PhD.
I was also interested in doing international work. In part because there’s a whole lot that can be done in terms of sharing knowledge and best practices we already have to solve real human problems. There’s a lot of stuff we can do, just bringing the current standard of care to middle and low-income countries. Or cooperating on hard scientific problems between governments and among governments, as opposed to individual researchers in an uncoordinated and hypercompetitive fashion. I felt there was a lot of space for improving scientific progress, but also bringing to bear things we have already achieved to solving important real human problems.
I had a notion of working in my background on cancer, organ failure, and organ transplantation. So, I had this grand idea that I would work on problems like non-infectious diseases in low-income countries, and instead, I ended up at the fisheries office at the Department of State…I decided to do it and it was a really great experience.
It checked a lot of boxes I was looking for. It gave me a new subject area, so I wasn’t bored. I was way behind and had to learn every day the way things work, particularly at the Dept of State. If you’re the science person, well, science is science. So, I had climate impacts on fisheries in my portfolio. I had human health concerns, food security, labor, and fisheries to consider. I had to have some understanding of how the biomass of fisheries is assessed and how stock assessments work.
Q: Meaning, you’re interested in how we get information, how it is relevant to your projects, and how to use it?
CB: Yes, exactly. Communicating this to policymakers, a lot of it is just communicating process and uncertainty, which are directly translatable. If you have a basic understanding of statistics, you understand probability and uncertainty, and can read the abstracts of a couple of papers…then you already know more than a lot of policymakers, and you can help translate. Like, what does the confidence interval of this thing mean? General scientific skills are definitely really translatable. The ability to digest technical material very quickly, and if an expert, at least to be able to explain the basic concept to someone else. That’s basically a journal club.
I also had to do things that were completely out of the scope of anything I had done before. For instance, within six months of being there, I was representing the United States in treaty organizations. That was a real blast.
Q: So, what are the responsibilities of your current job at the State Department?
CB: I’m a contractor and basically, I manage grants to do development work related to ocean policy. I am the first point of contact for current grantees that have questions about implementations; changes to budgets, personnel, disruptions due to COVID-19, etc. I handle triage and any time there needs to be modifications to a scope of work, I will draft those and negotiate them with grantees before they go to the people that can approve those changes. I draft public diplomacy and outreach materials based on what our awardees have been doing. I draft the announcements for funding (a.k.a. notices of funding opportunity). I select the panelists for the panel review, coordinate the entire review process, notify the recipients that they have been successful or not. I do all the grunt work. I analyze the progress reports, including indicator data. For example, a report might say “we targeted we were going to train twelve people to manage marine protected areas in the next six months.” Then you read the reports, you ask for what they’ve done, ask for clarification, and you write up formal reports that get included in the report.
Q: Who do you find yourself interacting with on a day-by-day? Do most people have their PhDs? Do they have PhDs in science? Do they have a traditional government job?
CB: It depends. At the State Department, I work in the Science Bureau, so there are actually a huge number of PhDs. Then, we also have foreign service officers that rotate to a new job every two to three years, where they rotate between foreign posts and HQ. So, there is a mix of long-term civil service people, many of which have PhDs in my bureau and are experts, and also the foreign service officers who are trained as generalists. It’s interesting coming into an environment like that as a fellow because on the one hand you have a PhD and are an expert on something. But, you may not be an expert on the thing you’re being asked to do. So, in some ways, you’re more like a foreign service officer. You’re a person of general intelligence, who has developed a set of tools for learning and explaining scientific and technical material to other people. You have to figure out how to get up to speed and do this job for a year or two, do it well enough you can make something out of it, and then figure out something more long term to do. As a fellow, I could look at these foreign service officers like a model. They could have been the environment officer two years ago in Bolivia, and now they’re doing counterterrorism work at HQ. You have to be a dedicated learner.
Q: Working for the State Department, does your work in science policy affect international work?
CB: We aim to support good science and best practices, but often we may want to be encouraging an ally to get into a certain line of work. So, we might work with an NGO in a particular country that is working on a priority issue to try and encourage the government of that country to be serious about that issue. So, there are a number of different priorities with the State Department foreign assistance award that obviously wouldn’t be in your normal NIH grant…We have multiple different objectives that could be present at the same time or in different awards. Sometimes the award might be more for development assistance-type work, but other times it might be for enhancing science cooperation with a foreign govt or NGO.
I can say that, in general, an environmental issue that has a lot of bipartisan support is marine debris. That has been a large focus of our programming. A large focus of what we’re trying to do is identify gaps in knowledge and find partners that can work to fill those gaps, and produce local data on marine debris problems.
Q: What are some fellowships or academia-policy bridge programs/ do you have any recommendations?
CB: I think the AAAS is just about the premier fellowship. Most fellowships are one year, it has the opportunity to go up to two to three years, it pays pretty well, and has good opportunities for staying on at some of the departments or agencies. It is a good steppingstone with a broad array of opportunities.
Q: Are there any other major organizations other than the ones you mentioned AAAS?
CB: There are a few. AAAS actually has a really good resource page for other fellowships. It is probably the best comprehensive resource for all science policy opportunities.
There is a fellowship called the Mirzayan.
Another major route for getting into policy is the presidential management fellowship (PMF). For years, that had a tight eligibility window. There was a move to create a different STEM track to be a little more lenient, as many people do a postdoc and then figure out they want to do something else. With the PMF, you are guaranteed to transition into a government position, so it is super competitive.
Keep in mind, many of these fellowships have restrictions on how close to your degree award date you are. AAAS you can be at any tier.
Q: Do you have any advice on training experiences postdocs could get for going into policy?
CB: You have to figure out what is available. There are often local options available. Maybe there is a science policy journal club. If there isn’t, found one. Look into professional societies. They often have similar small effort programs that will let you stay in your current position, similar to what I did with AAI. You can also get involved in local politics. If you have kids it could be the school board. If you don’t, it could be any other municipal issues. But, find a way to expose yourself to some part of what is actually a very broad category of things that constitute policy. Any number of issues that some linkage to science. And get involved and see whether you like it and if it sparks something. In part, find opportunities to see if you actually find it interesting, as well as give yourself a bit of credibility that you’ve actually sought out some experience.
With AAAS the intention is not to take people who are already policy experts and put them in their program. It is to do an exchange and to bring science into the government, but also teach scientists about the policymaking process. So, you don’t need to be an expert, but it often helps to have some sort of proof that you have a serious interest.
It could be that you founded a science policy journal club or help someone run for city council. Think about what your interests are, and think about are there any natural intersections you can pursue before leaving the lab. That includes just asking around. Do informational interviews. Find people (like me) and see if they’re interested in a virtual coffee.
CB: If I could give one bit of advice: Do a lot of thinking about what you like, what interests you, and what your ultimate goal is. And have that be a framework for what opportunities you explore. That’s necessary, but I think you also need to be open to opportunities that you hadn’t initially envisioned. Be open-minded.
It’s helpful to have that framework for “what is it you like, what do I want to do, and where do I want to be?” When things come along, as long as they’re not completely antithetical to your interests or redlines, be open to taking things that aren’t exactly what you were thinking because no one has a monolithic career path, at this point anyway. Even if it may be a detour, it will probably take you farther forward than it will sideways and may open you up to something you never even thought about.
Chat with an Expert...Dr. Matthew Laurens
Archana Gopalakrishnan
Approximately 35 percent of the COVID-19 vaccine doses allocated for hospitals in Maryland have been administered to health care professionals. Operation Warp Speed has been underway all over the nation since December 2020 to ensure the safe distribution of the vaccine in an effective manner. Dr. Matthew Laurens is one of the principal investigators for the clinical trial testing the Moderna mRNA-1273 vaccine, at UMSOM’s Center for Vaccine Development and Global Health (CVD). He discussed the various stages of this vaccine development and the policies involved in moving this forward.
Q: Could you provide a brief overlay of what you do and how you came to be involved with the (Coronavirus Efficacy) COVE study with Moderna?
ML: I am an infectious diseases physician and researcher, focusing on clinical trials of vaccines against malaria, typhoid, and other infectious disease threats that disproportionately affect populations living in low and middle-income countries. As my work focuses on vaccine studies, I was asked to help lead the activities for the Moderna mRNA-1273 vaccine trial as part of our University’s participation as an NIH Vaccine and Treatment Evaluation Unit (VTEU) site. Our University’s Center for Vaccine Development is one of the ten VTEU network sites nationwide that provide a ready resource to the NIH for conducting clinical trials of vaccines and treatments for infectious diseases.
Q: In developing a vaccine what are the steps taken to ensure safety and efficacy? Is there a global standard to this or do countries have independent policy standards?
ML: Our work in the Moderna mRNA-1273 vaccine trial has focused on safely testing this vaccine, documenting the vaccine’s safety profile, and prioritizing our participant’s well-being. We have followed every step of documenting any vaccine side effects and remained in close contact with participants via cell phone availability 24/7, email, electronic diary records kept by participants for a week after vaccinations, and routine follow-up phone calls and in-person visits. By being constantly available for our study participants, this facilitated all of our work to diagnose and document any COVID-19 illnesses that occurred in vaccine and placebo recipients, thus contributing toward measurement of vaccine efficacy. All of our research followed international guidelines for the ethical conduct of clinical trials including those outlined in the Declaration of Helsinki. We treat all of our participants with respect, and this facilitates dialogue and open communication, permitting us to collect important safety and efficacy endpoint data.
WHO SAGE (Strategic Advisory Group of Experts on Immunization) makes recommendations to the WHO on global policies and strategies. Within SAGE is a COVID-19 working group that has provided guidance on measures to take during the pandemic. Most recently, WHO SAGE developed critical issues policy questions for COVID-19 vaccines policy making, a roadmap for COVID-19 vaccines prioritization in the context of limited supply, and an evidence framework for COVID-19 vaccine recommendations.
Q: If these vaccines are going to be available at no cost to the public, how do companies profit?
ML: Companies that are part of the US Operation Warp Speed entered into different public-private partnership agreements with the US government. These companies assumed a certain amount of financial risk to begin large-scale manufacturing and production of vaccines before all safety and efficacy data was available. This financial risk was offset by the public funding and support, including pre-orders for vaccines and market commitments from multiple countries.
Q: Who approves a vaccine for mass global deployment? In the initial months when dosage shortages exist, how do health authorities decide who will get vaccinated?
ML: Countries that do not have their own FDA equivalent typically look to the WHO for guidance. These countries rely on the WHO’s technical expertise and follow the framework for vaccine distribution and prioritization that the WHO has developed. Individual states have received federal funding to aid in the delivery of vaccines, and each state has used these funds based on local needs and priorities.
Q: With a continuing rise in anti-vaccine sentiments and vaccine hesitancy, can changes in science policy help increase the confidence the public has in scientists and/or the scientific process?
ML: Transparency in the entire scientific process is a wonderful way to increase confidence in vaccines, but this is not enough. We need trusted community members to also promote vaccines, explaining the benefits vaccines provide as a tool to fight the pandemic. These trusted members of the community can be individuals in healthcare, but should also have representation from mainstream and social media channels so that individuals at the highest risk for COVID-19 transmission and complications receive the message that vaccines are safe and effective against the disease. Science policy should therefore prioritize communication measures to effectively reach these vulnerable populations. We still have work to do on this front.
January/February Career Development Events
Scientific Writing Seminar Series: Developing Tables, Figures, and Graphs for Your Research Paper. Jan 14th, 9-10 AM. Register here.
UMB Flu Vaccine Clinic - Held on the second floor of the SMC Campus Center, this clinic also offers asymptomatic COVID-19 diagnostic testing. Jan 15th, 9 AM to 1 PM, register here.
Faculty Research at a Predominantly Undergraduate Institution (PUI): A Panel of Scientists - Virtual workshop featuring faculty from Towson University and Salisbury University discussing what it’s like to be a faculty member at a predominantly undergraduate institution. Jan 15th, 1-3 PM. Register here.
Applications of Humanized Mouse Models Across Broad Therapeutics Areas - CIBR Lunch & Learn event. Jan 19th, 12-1 PM. Register here.
"Chalk Talks and More - In the Midst of the Pandemic"- PDAC Zoom event. Hear the journey of four new UMSOM faculty members and how they became a part of the UMB community in 2020. Jan 26th, 12-1 PM. Register here.
Managing Your Research Program Seminar Series: Time Management - Including When to Say “Yes” and How and When to Say “No”. Jan 26th, 9-10 AM. Register here.
Research Skills Seminars: Giving a Good Research Talk - Jan 28th, 9-10 AM. Register here.
Strategy for a Successful Postdoc: Planning Your Path - Timeline for a Successful Postdoc - Feb 4th, 12-1 PM. Register here.
Mentoring Training Workshops for Students and Postdocs: Introduction and Effective Communication - Feb 8th, 12-1:30 PM. More information coming via email.
Mentoring Training Workshops for Students and Postdocs: Aligning Expectations and Assessing Understanding - Feb 15th, 12-1:30 PM. More information coming via email.
Grant Writing Class: Overview and Introductions for Grant Writing/Specific Aims - Feb 17th, 9-10 AM. Register here. More information can be found in the email sent by Renee Cockerham.
Tools for a Successful Postdoc: How to Effectively Communicate Your Science Panel - Feb 18th, 12-1 PM. Register here. More information coming via email).
Scientific Writing Seminar Series: Writing Effective Titles and Abstracts - Feb 18th, 9-10 AM. Register here.
Grant Writing Class: Research Strategy Section- Approach - Feb 24th, 9-10 AM. Register here.
More information can be found in the email sent by Renee Cockerham.
Nerdy Humor
"Piled Higher and Deeper" by Jorge Cham