Transplant Recipients Experience Limited Protection With Primary COVID-19 Vaccination Series, but Third Dose Boosts Response

BOSTON – Transplant recipients must take life-long immunosuppressive medications to prevent rejection, but these drugs can compromise the effectiveness of vaccines.

New research indicates that lung and heart transplant recipients experienced diminished and delayed antibody responses to the first two COVID-19 mRNA vaccine doses, but most developed significantly better responses following a third dose. Cross-protection of vaccination against SARS-CoV-2 viral variants was only partial, however.

The study, which was conducted by a team led by investigators at Massachusetts General Hospital (MGH) and is published in Open Forum Infectious Diseases, included 18 lung transplant recipients, 17 heart transplant recipients, 7 non–lung-transplanted patients with cystic fibrosis, and 12 healthy individuals (all without SARS-CoV-2 infection).

Scientists measured blood levels of antibodies against different variants of SARS-CoV-2 at various time points after a primary mRNA COVID-19 vaccination series.

Among healthy controls, strong antibody responses to the SARS-CoV-2 spike protein arose immediately following vaccination and displayed cross-neutralization against all variants.

Among heart and lung transplant recipients, increases in antibody concentrations occurred only gradually following the first two vaccine doses, and cross-neutralization was less than 10% against variants (and completely absent against the Omicron variant).

Most (73%) transplant recipients developed a significant response after the third vaccine dose, however, reaching levels comparable to those of healthy controls, with improved but lower level responses against Beta, Gamma, and Omicron variants. Responses of non–lung-transplanted cystic fibrosis patients paralleled those of healthy controls. 

“Our findings highlight that effective protection of most transplant recipients is achievable but requires the recommended additional doses of vaccine. However, for most individuals, cross-protection of their responses to currently circulating immune-evasive SARS-CoV-2 variants is attenuated. The multiple subsequent vaccine doses recommended for transplant recipients are likely critical for maintaining immunity,” says co–senior author Marcia B. Goldberg, MD, an investigator in the Division of Infectious Diseases at MGH and a professor in the Departments of Medicine and Microbiology at Harvard Medical School. “Next steps are to analyze the cellular immune responses of solid organ transplant recipients over the same longitudinal time frame.”

Additional co-authors include May Y. Liew, Josh I. Mathews, Amy Li, Rohan Singh, Salvador A. Jaramillo, Zoe F. Weiss, Kathryn Bowman, Pierre O. Ankomah, Fadi Ghantous, Gregory D. Lewis, Isabel Neuringer, Natasha Bitar, Taryn Lipiner, Anand S. Dighe, Camille N. Kotton, Michael S. Seaman, and co–senior author Jacob E. Lemieux.

This work was supported by a Clinical Research Award from the Cystic Fibrosis Foundation (002211321, to MBG), a Mendez National Institute of Transplantation Foundation award (to MBG), and an American Lung Association COVID-19 Action Initiative Special Research Award (to MBG).

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.