Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response

Abstract

Background We report the results of a prospective study on the immunogenicity of a 3rd dose of BNT162b2 in thoracic organ recipients with no or minimal response following a two-dose BNT162b2 vaccination scheme. Methods A total of 243 transplant recipients received a homologue 3rd dose. Anti-SARS-CoV2-immunoglobulins (IgGs) were monitored immediately before (T1), 4 weeks (T2) as well as 2 and 4 months after the 3rd dose. Neutralizing antibody capacity (NAC) was determined at T2. To reveal predictors for detectable humoral response, patients were divided into a positive response group (n = 129) based on the combined criteria of IgGs and NAC above the defined cut-offs at T2—and a group with negative response (n = 114), with both, IgGs and NAC beyond the cut-offs. Results The 3rd dose induced a positive humoral response in 53% of patients at T2, 47% were still non-responsive. Sero-positivity was significantly stronger in patients who presented with weak, but detectable IgGs already prior to the booster (T1), when compared to those with no detectable response at T1. Multivariable analysis identified age > 55 years, a period since transplantation < 2 years, a reduced glomerular filtration rate, a triple immunosuppressive regimen, and the use of tacrolimus and of mycophenolate as independent risk factors for lack of humoral response. Conclusions Our data indicate that a lack of immunogenicity is linked to the type and extent of maintenance immunosuppression. The necessity of the cumulative immunosuppressive regimen might individually be questioned and possibly be reduced to enhance the chance of an immune response following an additional booster dose.

Cowpox to COVID: History of vaccination in the immunocompromised host

“… 98 Similar factors have been identified in other studies as associated with vaccine response 70,72,73,99 and also identified receipt within 12 months of ATG or rituximab as associated with impaired response 70 . In studies focusing on heart and lung transplant recipients, age and antimetabolite use were again found to be associated, including an identification of moderate and high dose MMFs (>1000 mg daily), but not low (<1000 mg daily) dose MMF, as associated with impaired response 77,100,101 . A meta‐analysis of factors important for SARS‐CoV‐2 vaccine response identified a negative impact of antimetabolite (OR 4.3 [95% CI 3.4–5.4]) and belatacept (OR 5.4 [95% CI 3.4–8.7]) use 102 .…”

Seroconversion after SARS‐CoV‐2 vaccination is protective against severe COVID‐19 disease in heart transplant recipients

“…Furthermore, a fourth vaccine dose resulted in seroconversion in a few more cases. Numerous studies confirmed that a third dose of vaccine increased antibody response against SARS‐CoV‐2 in solid organ transplant recipients 11–13,25–29 . In light of these findings, it became evident that booster vaccine doses would be essential in the prevention strategy against SARS‐CoV‐2.…”

“…In light of these findings, it became evident that booster vaccine doses would be essential in the prevention strategy against SARS‐CoV‐2. However, several recipients had insufficient immune response against SARS‐CoV‐2 indicating that alternative strategies may be needed to improve protection in some immunocompromised patients 26–28 . For those solid organ transplant recipients who do not have sufficient antibody titers after three vaccines, the ESOT suggests the administration of additional booster vaccine doses or the consideration of pre‐exposure prophylaxis with monoclonal antibodies 14…”

“…Numerous studies confirmed that a third dose of vaccine increased antibody response against SARS-CoV-2 in solid organ transplant recipients. [11][12][13][25][26][27][28][29] In light of these findings, it became evident that booster vaccine doses would be essential in the prevention strategy against SARS-CoV-2. However, several recipients had insufficient immune response against SARS-CoV-2 indicating that alternative strategies may be needed to improve protection in some immunocompromised patients.…”

“…In vaccinated HTX recipients, the weaker immune response was related to older age, 10,23,28 male sex, 23 vaccination within the first 23 or second 28 year after HTX and MMF or MPA immunosuppressant therapy 10,12,23,28 . Studies of solid organ transplant recipients showed that predictive factors for humoral response after vaccination were male sex, a longer period between transplantation and vaccination, living donor status, and liver transplantation.…”