Institute of Human Virology at the University of Maryland School of Maryland scientists, who are also members of the Global Virus Network (GVN), a coalition comprised of human and animal virologists from 63 Centers of Excellence and 11 Affiliates in 35 countries, and colleagues today published a perspective proposing that live attenuated vaccines (LAVs), such as those for tuberculosis, measles, and polio, may induce protective innate immunity that mitigate other infectious diseases, triggering the human body’s natural emergency response to infections including COVID-19 as well as future pandemic threats.
The scientists suggest that LAVs prospectively might offer a vital tool to bend the pandemic curve, averting the exhaustion of public health resources and preventing needless deaths, and merit being studied. The perspective was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
“A review of epidemiological, clinical and biological evidence suggests that induction of innate immunity by existing LAVs, that is, the broadly effective vaccines, can protect against unrelated infections such as coronavirus, and could be used to control epidemics caused by emerging pathogens,” said Dr. Robert Gallo, The Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-Founder & Director of the Institute of Human Virology at the University of Maryland School of Medicine, and Co-Founder & Chairman of the International Scientific Leadership Board of the Global Virus Network.
Dr. Gallo said, “This approach is worthy of prompt further study due to the probability of future pandemics. This could be a stop-gap before specific vaccines are made. But even in the current pandemic they may be of use in non-affluent nations where the specific vaccines are not available.
“Our innate immune response is the first line of defense against invading, new pathogens. The outcome of any infection depends on the race between the pathogen and the host defense systems. The innate immunity and enhancing defense pathways provided by widely-used and well-recognized vaccines could substantially mitigate, or even prevent, infection from other pathogens such as SARS-CoV-2. This is especially valuable because LAVs can fill the gap until specific vaccines are available and in particular when they have not reached certain countries globally.”
“We very actively support the marvelous COVID-19-specific vaccines, and nothing in this publication conflicts with the development and use of these effective vaccines,” said Dr. Michael Avidan of the Department of Anesthesiology, Washington University, St Louis, MO. “We are suggesting that in the absence or availability of pathogen-specific vaccines, particularly in the beginning phase of a pandemic, that LAVs be rigorously tested to determine whether they can control infection and disease progression.”
“LAVs are safe, cheap and proven effective strategy to curtail the COVID-19 pandemic in two ways,” said Dr. Shyam Kottilil, Professor of Medicine and Director, Division of Clinical Care and Research, Institute of Human Virology at the University of Maryland School of Medicine, GVN Center of Excellence. “By offering immediate protection against infection with SARS CoV-2 mediated by enhanced innate immunity and boosting immune response to traditional vaccine against COVID19 working as an adjuvant.”
“Even in the case of a microorganism such as SARS-CoV-2, for which we have been able to develop vaccines fairly quickly, it is still a minimum of one and a half to two years until a safe and effective vaccine can be produced, tested, distributed, and delivered globally,” said Dr. Dean Jamison, a leading global health economist of the Institute for Global Health Sciences, University of California, and the GVN. “In this period, countless lives have been lost and economic havoc has been unleashed in the world economy. This could be even more tragic in the case of a future pandemic for which the development of a vaccine is more challenging, transmission is more rapid, or herd immunity more difficult to achieve. LAVs that stimulate innate immunity could serve as a stop-gap until an effective vaccine is widely available.”
“Besides protecting against infection, innate immunity stimulation also has the potential to be used therapeutically in the early stages of disease, as well as to boost the effectiveness of vaccines that promote a specific adaptive immune response. This potential, while theoretical, is also worthy of further study,” said Dr. Konstantin Chumakov, Associate Director for Research for the U.S. Food and Drug Administration’s (FDA) Office of Vaccines Research and Review, and a GVN Center Director. “As we wrote last year in a perspective published in Science, studies with the oral poliovirus vaccine (OPV) from the 1960s and 1970s demonstrated nonspecific immune protection and found that OPV reduced the incidence of seasonal influenza and acute respiratory disease.”
In 2014, a World Health Organization (WHO)-commissioned review at the recommendation of the Strategic Advisory Group of Experts on vaccines (SAGE) concluded that LAVs reduced child mortality by more than expected. The same patterns were observed in high-income settings, including in the U.S., as having a live vaccine as the most recent vaccine being associated with a halving of the risk of hospitalization for non-targeted infections. The WHO review advised more research regarding the beneficial heterologous effects of LAVs; to date, no such WHO studies have been conducted.
The authors said that because of the huge toll that the current pandemic has taken on a global basis, looking into all possible options is essential. Despite the unprecedented brief time that it took to develop, test and deliver the current vaccines, it still took a year and a half and if LAVs could help stimulate innate immunity, they could help delay the global impact of a new pandemic while a new vaccine is being developed.
“There is immense readiness and massive financial support to develop and deliver the novel specific vaccines, but very little to test LAVs for use during a pandemic, despite their potential to prevent needless suffering and help mitigate social and economic carnage in any future pandemic. There are even some advantages in that they work very promptly, are low cost and likely to be readily available. Furthermore, their safety profile is often well-established. But we must acknowledge there are likely limitations because they do not last very long, perhaps only a few months, said Dr. Gallo.
“My esteemed colleagues and I are urgently calling on governments, philanthropy and non-profit foundations to support testing of an LAV strategy to determine whether LAVs can protect high-risk populations such as healthcare workers and the elderly as well as low-income populations worldwide, thereby reducing social and economic inequities.”
In addition to Dr. Robert Gallo, Dr. Konstantin Chumakov, Dr. Michael Avidan, Dr. Shyam Kottilil, and Dr. Dean Jamison, the authors of the PNAS viewpoint include Dr. Christine Benn of the Department of Clinical Research, GVN Center of Excellence, University of Southern Denmark; Dr. Mihai Netea of the Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, a GVN Center of Excellence; Dr. Annie Sparrow of the Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai; Dr. Stefano Bertozzi of the School of Public Health, University of California at Berkeley and the GVN; Dr. Lawrence Blatt of Aligos Therapeutics and the GVN; Dr. Angela Chang of the Danish Institute for Advanced Study, University of Southern Denmark; and, Dr. Shabaana Khader of the Department of Molecular Microbiology, Washington University in St. Louis School of Medicine.
“LAVs against tuberculosis and smallpox have been associated with better long-term survival,” said Dr. Christine Benn of the Department of Clinical Research, GVN Center of Excellence, University of Southern Denmark. “For example, OPV campaigns in West Africa have been associated with a 25% reduction in all-cause mortality, with each additional dose reducing mortality by a further 14%.”
“Several basic science observations make clear the central importance of innate immunity in controlling coronaviruses including SARS-1, SARS-CoV-2, and MERS,” said Dr. Mihai Netea of the Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, a GVN Center of Excellence. “Further, control of coronaviruses by bats is largely associated with an appropriate balancing of innate immune responses between resistance and tolerance.”
“It is critically important from both scientific and public health perspectives that we complete rigorous trials evaluating the effectiveness of LAVs in preventing COVID-19 or mitigating its severity,” said Dr. Annie Sparrow of the Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai. “The findings from these trials will inform if, and how, we could incorporate LAVs into our toolkit against future pandemics.”
About the Institute of Human Virology
Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland, and the University of Maryland Medical System, the IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology, and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders – most notably, HIV the virus that causes AIDS. For more information, visit www.ihv.org and follow us on Twitter @IHVmaryland.
