New Study Reveals Insights into Lack of Durability in COVID Antibody Response to Infections & Vaccines

Photo: Co-authors, George Lewis, PhD (left) and Mohammad Sajadi, PhD are researchers at the Institute of Human Virology (IHV)

Researchers at the IHV at the UMSOM published a new study in the Journal of Infectious Diseases investigating the short-lived antibody response following SARS-CoV-2, the virus that causes COVID.

Long-lived plasma cells are responsible for durable antibody responses that persist for decades after immunization or infection.  For example, infection with measles, mumps, rubella, or immunization with vaccines against these contagions elicit antibody responses that can last for years or decades.  By contrast, immunity against COVID from either a natural infection or a vaccine confers a much shorter-lived antibody response, only up to a few years at most. The mechanism underlying this problem, however, remained unknown. 

“We know long-lived plasma cells can produce antibodies against specific pathogens for decades, so we wanted to investigate their role in COVID infection,” said study co-author Mohammad Sajadi, MD, Associate Professor of Medicine, Division of Clinical Care and Research, Institute of Human Virology.

The study by Dr. Sajadi and his colleagues examined the contribution of long-lived plasma cells in the bone marrow to anti-spike antibodies after COVID infection.  They studied 20 individuals with a history of COVID infection but no vaccination. Bone marrow aspirates and plasma samples were analyzed to characterize antibody responses. The research found a deficient generation of spike-specific long-lived plasma cells in the bone marrow, offering insight into the short duration of antibody responses observed in recovering COVID patients.

“The rapid waning of spike-specific antibodies we observed indicates a lack of durable antibody production after natural infection,” said study co-author George Lewis, PhD, director of the Division of Vaccine Research, Institute of Human Virology. “This appears to be due to insufficient generation of long-lived plasma cells that would sustain antibody levels, a phenomenon we’ve noted before with certain viruses.”

Ten years ago, the researchers discussed the possible mechanisms for this problem with regards to HIV in a peer-reviewed publication and have been working on it since. (Like COVID vaccines, experimental HIV vaccines also confer short-lived immunity.) Their work on the poor persistence of antibody responses to the SARS-CoV-2 spike protein shows that the antibody persistence problem extends to COVID as well and that it is likely due to lack of long-lived antibody-secreting cells in the bone marrow.

Shyam Kottilil, PhD, Interim IHV Director, added, “Sustained antibody responses to viral infections are critical for vaccine development and long-term immunity. The presence of long-lived plasma cells in bone marrow is a crucial component for the generation of prolonged effective antiviral immunity. This study by Drs. Sajadi and Lewis and colleagues provide vital information about protracted immunity to COVID, which is a breakthrough in our understanding of antiviral immunity due to COVID and other viruses.” 

The researchers say the findings will help inform the development of vaccines and therapeutics that can induce robust long-term antibody production against SARS-CoV-2 and HIV. New studies have been designed in people to work out the cellular and molecular basis of this problem.

“This intriguing new study provides a possible explanation for why antibody responses to SARS-CoV-2 decay quickly,” said Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore. “Future studies will be key to further investigate the cellular and molecular basis of why SARS-CoV-2 does not elicit long lived antibody secreting cells specific for the SARS-CoV-2 spike protein with the ultimate goal of correcting this deficit in future vaccine designs.” 

The team aims to secure further funding to continue pursuing this critical area of vaccine research.

“We were fortunate to be able to study this problem in context of first exposure to a new human pathogen and disease,” said Dr. Sajadi. “We are grateful to our volunteer participants and colleagues, especially co-first authors Drs. Zahra Rikhtegaran Tehrani and Parham Habibzadeh, as well as Robin Flinko, whose efforts made this impactful study possible.”

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 ihv.org and follow us on Twitter @IHVmaryland.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu.