High-Dose Influenza Vaccination May Benefit Transplant Recipients

Flu Vaccine
Flu Vaccine
Double-dose influenza vaccine is safe and may increase antibody response in solid-organ transplant recipients

Double-dose influenza vaccine is safe and may increase antibody response in solid-organ transplant recipients, according to a study published in Vaccine.

Influenza infection increases the risk for bacterial pneumonia, intensive care admission, and death in patients who have received solid-organ transplants. Further, evidence links influenza infection with an increased risk for allograft rejection and inferior allograft survival. Thus, as a preventative strategy, an annual vaccination containing 15 µg of hemagglutinin antigen per viral strain is strongly recommended. To improve vaccine immunogenicity in solid-organ transplant recipients, high-dose vaccine containing 60 µg hemagglutinin antigen per influenza strain enhances immunogenicity.

Since this high-dose vaccine is only available in North America, an alternative strategy of 2 simultaneous injections of the standard vaccine (15 µg each) may also increase the amount of influenza antigens delivered with vaccination, but has not been tested in patients who have received solid-organ transplants. Therefore, this open-label randomized study (ClinicalTrials.gov identifier: NCT02746783) aimed to compare the immunogenicity and safety of 1 (15 µg of hemagglutinin antigen per strain, standard dose) vs 2 simultaneous intramuscular injections (30 µg of hemagglutinin antigen per strain, double-dose) of a commercially available 2014/2015 trivalent inactivated influenza vaccine containing 15 µg of hemagglutinin antigen per strain in kidney and liver transplant recipients.

The study included 79 patients who received solid-organ transplant between 2014 and 2015, 63 of whom received kidney transplants and 16 received liver transplants. Of these, 40 patients (7 liver and 33 kidney transplantation cases) received the double-dose and 39 patients (9 liver and 30 kidney transplantation cases) received the standard dose vaccine. Baseline characteristics were similar in both groups and the median time from transplantation was 40 and 23 months in the double-dose and standard-dose groups, respectively. Most patients had received the influenza vaccine during the previous influenza season (82.5% in the double-dose group and 79.5% in the standard-dose group). Vaccine response was defined as seroconversion to at least 1 viral strain 2 weeks after vaccination and seroprotection as a titer ≥40.

By and large, vaccine response was poor (32.9% in the entire study population) and below the standard of efficacy of the European Medicines Agency (40%). There was a non-significant increase of 14% in vaccine response rate and a trend toward enhanced immunogenicity. Results showed that 40% of patients in the double-dose group compared to 26% of patients in the standard-dose group responded to the vaccine (P =.174). Further, in the double-dose group more patients were seroprotected to all viral strains after vaccination (88% vs 69%; P =.048). Post-vaccination geometric mean titers of antibodies were 131.9 vs 89.7 (P =.187) for H1N1, 185.4 vs 138.7 (P =.182) for H3N2, and 96.6 vs 68.8 (P =.081) for influenza B in the double-dose vs standard dose groups. Most of the adverse effects were mild in both groups, and no vaccine-related severe adverse events were observed.

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Overall, the study authors concluded, “While increasing the amount of antigens delivered with vaccination from 15 to 30 µg did not significantly improve the pre-established definition for vaccine response, the observed trend toward a better immunogenicity with the double-dose vaccination is encouraging and adds more evidence for the use of high-dose influenza vaccine in solid-organ transplant.”


Mombelli M, Rettby N, Perreau M, Pascual M, Pantaleo G, Manuel O. Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: a randomized controlled trial [published online September 1, 2018]. Vaccine. doi:10.1016/j.vaccine.2018.08.057