Enhanced Immune Response after a Second Dose of an AS03-Adjuvanted H1N1 Influenza A Vaccine in Patients after Hematopoietic Stem Cell Transplantation

Abstract

Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and ≥ 4-fold increase in AB titer 21 days after vaccination. Seventeen patients (14 allogeneic, 3 autologous HSCT) received 1 dose and 11 of these patients 2 doses of the vaccine. The rate of seroconversion was 41.2% (95% confidence interval [CI] 18.4-67.1) after the first and 81.8% (95% CI 48.2-97.7) after the second dose. Patients who failed to seroconvert after 1 dose of the vaccine were more likely to receive any immunosuppressive agent (P = .003), but time elapsed after or type of HSCT, age, sex, or chronic graft-versus-host disease was not different when compared to patients with seroconversion. In patients with hematologic malignancies after HSCT the rate of seroconversion after a first dose of an adjuvanted H1N1 influenza A vaccine was poor, but increased after a second dose.

Vaccination against pandemic H1N1 (2009) in patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis

“…One dose of seasonal influenza A/H1N1 vaccine is highly immunogenic in adults, while two doses will probably be needed in children younger than 9 years [21]. Recent reports support the benefit of repeated H1N1 (2009) vaccination, indicating significantly increased HI titers in response to the first and second vaccination [15,27].…”

Immune reconstitution after hematopoietic cell transplantation

“…When humoral immunity returns, patients first respond to protein recall antigens and only later to polysaccharide antigens or protein neoantigens [111][112][113][114][115][116]. In addition, achieving protective antibody titers often requires a second or third vaccination [117,118].…”

Seasonal influenza vaccination of high-risk adults

“…In this case, a second dose is recommended four weeks after the first. The benefit of this second dose was shown during the 2009 pandemic [126]. Influenza vaccination guidelines in most countries specifically target this population, but vaccine coverage remains below recommended levels ( Table 1).…”