High Humoral Response Frequent in Allogenic HSCT Patients After Second COVID Vaccine Dose

By Marilynn Larkin

July 27, 2021

NEW YORK (Reuters Health) - In allogenic hematopoietic stem cell transplant (HSCT) recipients, "frequent and high levels" of humoral responses were seen after two doses of the BNT162b2 (Pfizer-/BioNTech) vaccine, researchers say.

As reported in The Lancet, Dr. Sebastien Maury of Hopital Henri Mondor in Creteil, France, and colleagues analyzed the immunogenicity of the BNT162b2 mRNA vaccine in 88 allogenic HSCT patients (median age, about 60; about 55%, men) who had received two doses, at a 4-week interval, at a median of 23 months after allogeneic HSCT.

Antibody (ab) quantification was performed centrally in the institutional virology hospital lab, Dr. Maury told Reuters Health by email. Specifically, the team used the IgG II Quant Assay (Abbot Laboratories, Wiesbaden, Germany) to quantify spike glycoprotein-specific IgG receptor-binding domain levels at a median of 28 days after the second vaccine dose.

IgG (S-RBD) titers could be quantified in 69 (78%) participants; was detected but not quantifiable in three participants (anti-S titer <21 arbitrary unit per mL); and was not detected in 16 participants (anti-S titer <6.8 AU/mL).

In addition, nucleoprotein-specific IgG was detected in seven of 88 participants, indicating previous SARS-CoV-2 exposure.

In comparing characteristics of patients with IgG(S-RBD) titers above and below 4,160 AU/mL, a time interval greater than 12 months between HSCT and vaccination, as well as the absolute lymphocyte count in peripheral blood above 1G/L at the time of vaccination, correlated with protective post-vaccination IgG(S-RBD) titers.

However, participants who had received systemic immunosuppressive drugs within three months of vaccination had subprotective titers.

In multivariable analysis, systemic immunosuppressive therapy within three months of vaccination, together with a lymphocyte count below 1 G/L in peripheral blood, remained independently correlated with low IgG(S-RBD) titers; the time interval between HSCT and vaccination was no longer a factor.

The authors conclude, "Our findings support the large-scale vaccination of allogeneic HSCT recipients, although additional multicenter and long-term studies are needed to specify the level of immunological protection against infection, also taking into account the effect of a third vaccine dose in non-responding patients."

Dr. Maury said his team is doing additional research "focusing on the correlation between humoral response to vaccination and protection against disease in this population."

Transplant surgeon Dr. Sham Dholakia, Chief Medical Officer at CareDx and leader of the development of the C19TxR registry for COVID tracking of transplant patients, commented in an email to Reuters Health.

"Overall morbidity and mortality in HSCT transplant may not be as high as documented within this article," he said. "Many citations (show) the overall HSCT population is very heterogenous, as shown by the wide range of time post-transplant, where the median is 23 months but could be anywhere from 3 months to 17 years. This makes the profile of patients variable."

"The biggest issue...is the time of the testing," he said. "Twenty-eight days is a very narrow window. There are data to show antibodies can decline within three months post-vaccine or take several months to be formed."

"The exact level of antibody titers is really important," he noted. "It is still unknown if they are IgG and/or IgM or if the T cells themselves having a response is enough to offer protection. There is also variance seen with age, which is important to capture."

"The use of ab thresholds needs a lot of work," he added. "Just because you have ab titers below a threshold does not mean you are not protected," although the levels may be used to decide who gets boosters first."

Further, he said, it will be important to understand the variation in kits used to measure antibodies, including newer methods that are fully quantitative.

"Learning how to use and interpret antibody titers needs a much larger sample size and systematic approach with regular intervals," Dr. Dholaka concluded.

SOURCE: https://bit.ly/3BEVbDv The Lancet, online July 13, 2021.