The CRS Community sprung into action upon the COVID-19 pandemic. To recognize all that is being done during this time, we have gathered some stories from scientists, researchers, and labs from around the world.
Exploring potential drug therapies for COVID-19
The Wasan Laboratory at the University of Saskatchewan is currently working with The Vaccine and Infectious Disease Organization - International Vaccine Centre (VIDO-InterVac; https://www.vido.org/news/) to perform testing of two small molecule drugs and a drug combination as a potential therapeutic for COVID-19. Following confirmatory in vitro studies, in vivo efficacy studies in an animal model of SARS-CoV2 infection at VIDO-InterVac will commence.
PI: Drs. Ellen Wasan, Kishor Wasan, Volker Gerdts
Dr. Kishor M. Wasan, R.Ph., Ph.D., FAAPS, FCAHS, FCSPS
Responding to the need for Personal Protective Equipment (PPE) and other safety items during the pandemic
Eneko Larrañeta1, Juan Dominguez-Robles1, Dimitrios A. Lamprou1
1School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK
In March 2020, the first outbreak of Covid-19 was announced in Northern Ireland (NI) and the virus then quickly started to spread. With the enormous shortage of personal protective equipment (PPE), staff at Queen’s University Belfast (QUB) wondered what they could do to help their colleagues in the healthcare professions and the local community in these exceptionally challenging times. Our team quickly responded by coming up with a pioneering programme to develop PPE and other items using 3D printers (3DP) that are normally used for research to manufacture drug delivery systems and medical devices. This also included designing and producing face-shields and ‘no-touch’ hand tools that can be used for safely opening doors, keypads, elevator buttons, and light switches (Figure 1). The School of Pharmacy (SoP) was the first to respond to the PPE shortage crisis in NI and all items were designed, produced and delivered free of charge. Due to the scale of the shortage, design and production ideas were also shared on social media to encourage others locally, nationally and internationally to respond.
The team initially engaged in conversations with the Belfast Healthcare Trust to ensure that understood the needs, and product specifications. We began by manufacturing face-shields for healthcare workers followed by ‘no-touch’ hand tools. These were rigorously tested to ensure that they were delivering the correct design, which would be safe, comfortable, and reusable from biodegradable material (PLA) in order to reduce the environmental impact. Over 1,500 face-shields and over 1,500 "no-touch" hand tools manufactured and delivered. With the sharing of design and production guidelines, the overall delivery of PPE can be estimated in thousands. This does not include the psychological benefits of healthcare staff feeling protected and much safer working amidst the deadly virus and ultimately saving lives and stopping the spread of infection.
Figure 1. Examples of 3D-printed face shield and door openers prepared by the SoP at QUB.
Acknowledgments
The authors thank the technical staff at the School of Pharmacy at QUB for all their support with 3DP during the pandemic and Belfast Trust for all their advice on PPE safety considerations.
Reference
Larrañeta E., Dominguez-Robles J., Lamprou D.A. (2020) Additive Manufacturing can assist in the fight against COVID-19 and other pandemics and impact on the global supply chain. 3D Printing and Additive Manufacturing. Ahead of Print. https://doi.org/10.1089/3dp.2020.0106
A USC approach for a new vaccine against COVID-19 based on mRNA
María José Alonso
The laboratory of María José Alonso at the University of Santiago de Compostela (USC) in collaboration with the clinical hospital of Barcelona (IDIBAPS), the University of Barcelona, the Institute of Biomedical Research of Barcelona (IRB), Pompeu Fabra University, the National Center for Biotechnology (CSIC) and the Free University of Brussels is working on the development of a new mRNA vaccine against COVID19.
The objective of Alonso’s laboratory is to produce a synthetic delivery vehicle based on biodegradable biomaterials, capable of transporting the mRNA molecules into the target cells and enabling the production of the antigen in the human body. mRNA vaccines are expected to be a promising alternative to conventional vaccines due to its rapid development, low manufacturing cost and safe administration.
Alonso’s Lab expertise in vaccines
Being trained in the early 90’s in Langer’s Lab, María Alonso and her team have been working on the development of new vaccines for 3 decades. Notably, under the support of the Bill &Melinda Gates Foundation, the WHO, the NIH, the European Commission, she has worked on the development of stable, single-dose vaccines and needle-free vaccines. Within this frame, she pioneered the engineering of PLA-PEG and also chitosan-based nanocarriers for nasal vaccination. The most recent developments of her lab are two HIV vaccine candidates, one of them based on multiple peptides, in collaboration with US and Canada, already proven in macaques. The other one is an mRNA vaccine candidate in collaboration with an European consortium.
The COVID19 vaccine project
The project has involved the use of artificial intelligence and computational methods to identify the parts of the virus that are capable of provoking a remarkable response in the immune system. Currently, the most promising mRNA molecules have been identified and will be manufactured in the next few weeks. The mRNA candidates will be incorporated into a viral or synthetic vector, in order to guarantee the stability of the RNA and favour its effective arrival in the immune system. The laboratory of Prof. Alonso has already produced a number of carriers that will be tested for the transport and efficient transfection of the selected mRNA.
Researchers Receive NIH Funds for Adjuvant Research to Boost Coronavirus Vaccines
Researchers have received funding from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, to screen and evaluate certain molecules known as adjuvants that may improve the ability of coronavirus vaccines to stimulate the immune system and generate appropriate responses necessary to protect the general population against the virus.
“The adjuvants that we are studying, known as pathogen-associated molecular patterns (PAMPs), are molecules often found in viruses and bacteria, and can efficiently stimulate our immune system,” explained Krishnendu Roy, a professor and Robert A. Milton Chair in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Most viruses have several of these molecules in them, and we are trying to mimic that multi-adjuvant structure.”
Adjuvants are used with some vaccines to help them create stronger protective immune responses in persons receiving the vaccine. The research team will screen a library of various adjuvant combinations to quickly identify those that may be most useful to enhance the effects of both protein- and RNA-based coronavirus vaccines under development.
“We are trying to understand how adjuvant combinations affect the vaccine response,” Roy said. “We will look at how the immune system shifts and changes with the adjuvant combinations. The ultimate goal is to determine how to generate the most effective, strongest, and most durable immune response against the virus. There are more than a hundred vaccine candidates being developed for the SARS-CoV-2 virus, which causes COVID-19, and it is likely that many will generate initial antibody responses. It remains to be seen how long those responses will last and whether they can generate appropriate immunological memory that protects against subsequent virus exposures in the long-term.”
The parent grant to Georgia Tech is part of a program called “Molecular Mechanisms of Combination Adjuvants (MMCA).” For the past four years, the agency has been supporting Roy and his research team to pursue studies to understand how adjuvants work, and this additional funding will allow them to apply their research to potential coronavirus vaccines.
For more coverage of Georgia Tech’s response to the coronavirus pandemic, please visit our Responding to COVID-19 page.
“It has been difficult to develop safe and durable vaccines against respiratory viruses,” explained Roy, who also directs the Center for ImmunoEngineering. “Over the past several years, we have been looking mostly at the basic science and understanding how the immune system integrates signals from multiple adjuvants to create a unified immune response in mammals. This new funding will allow us to pursue more translational aspects related to COVID-19 and provide the scientific community with potentially new tools to fight this devastating pandemic.”
The team has developed a technique that uses micron- and nanometer-scale polymer particles to present both the vaccine antigen and adjuvant compounds to the mammalian immune system. The medical polymer that is the basis for the particles is used for other purposes in the body.
The synthetic particles, which Roy’s team calls pathogen-like particles (PLPs), are designed to mimic real pathogens in terms of how they elicit immune responses – without causing infection. “They have an antigen and multiple synergistic adjuvants on a particle-structure that is very similar to how native pathogens present these molecules to our immune system,” he said.
The PLPs combined with adjuvants encourage the immune system to develop antibodies and T cell responses that can battle the real pathogen if it attacks. Having existing antibodies and the appropriate virus-fighting T cells to the novel coronavirus will enable the body’s immune system to respond quickly to the threat of infection and potentially destroy the virus quickly.
The researchers will first evaluate how the adjuvants affect the interaction of specific immune cells, called dendritic cells and macrophages, with T cells – a key component of generating immune system response – and then follow up with animal studies using the promising combinations. Whether or not a vaccine can be created that will provide long-term protective immunity against the coronavirus is still an open question in the research community, and Roy said the research into adjuvants will help provide new tools to answer that question.
“Part of the knowledge gap right now is that we don’t know how the immune system is influenced by various adjuvants,” he said. “We need to look at how the vaccine formulations, our particles and the adjuvants affect T cell proliferation and T cell response, and how we can optimize that response to generate durable immunity.”
The adjuvant Alum has been used since the 1930s to boost the action of the immune system as it responds to antigens in vaccines that elicit protection against many pathogens. However, for those pathogens that require alternative adjuvants, only a few other adjuvants are currently used in commercial vaccines. Research on modern adjuvants aims to understand the way they specifically activate our immune systems and can be designed to protect against infections. Another approach is to find out if combinations of adjuvants are safe and more effective than a single adjuvant providing highly effective and long-lasting protective immunity.
Roy and his team will be evaluating existing adjuvants in combination, along with potential protein and RNA-based antigens currently under evaluation. The goal is to develop novel combinations of current adjuvants, including adjuvants approved for use and others that are still in development. “In this work, the strategy is to take existing platforms and see how we can pivot them to understand how to make the COVID vaccines better, and do it rapidly.”
As with other research into potential coronavirus vaccines, the work is being accelerated with the goal of creating a safe and effective vaccine against the pandemic virus as soon as possible.
“There are multiple efforts that the NIH and others are funding to really accelerate the pace of the work to see how many different approaches we can come up with and to evaluate the differences,” Roy said. “The goal is to determine what data we can generate very quickly to move toward a successful vaccine that is safe, durable, affordable, scalable, and effective. Evaluating different approaches will help increase the likelihood that we’ll find one or more that meet these criteria.”
This research is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under supplemental funding to award number U01AI124270. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
