Background:

Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. However, influenza vaccine may have the added benefit of inducing a cross-reactive immune response to viral strains not found in the vaccine. This is termed heterologous immunity and has not been previously assessed in transplant patients. Heterologous immunity has important implications for vaccine efficacy. Adjuvanted vaccines have been proposed as better inducers of heterologous immunity. We evaluated heterologous immune response to adjuvanted vs. non-adjuvanted influenza vaccine in transplant recipients.

Methods:

Pre- and post-vaccination sera from kidney transplant recipients (n=60) enrolled in a 2012-13 RCT of MF59-adjuvanted vs. nonadjuvanted influenza vaccine underwent testing by Hemagglutination inhibition assay for heterologous strains (i.e. strains not present in vaccine): A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2), B/Brisbane/60/2008. Seroprotection was defined as a heterologous strain-specific antibody titer ≥40 and seroconversion was a 4-fold rise in titer.

Results:

Baseline demographics and immunosuppression were similar in the adjuvanted and non-adjuvanted groups. Median time from transplant was 8.1 (0.73-33) years. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 23.3 to 77.3, p<0.001; H3N2: 80.0 to 136.1, p<0.001; B: 13.3 to 19.5, p<0.001). Baseline levels of seroprotection to heterovariant-A/H1N1, heterovariant-A/H3N2, and heterovariant-B were 48.3%, 78.3%, and 25% respectively. These increased to 78.3%, 88.3%, 38.3% after vaccination. Seroconversion rates were 41.7%, 16.7%, 13.3%. Seroconversion to at least one heterovariant-strain was 46.7%. No immunogenicity differences were seen in the adjuvanted vs. nonadjuvanted groups. Patients were more likely to seroconvert for a cross-reactive antigen if they seroconverted for the specific vaccine antigen. For example, seroconversion to heterovariant-A/H1N1 was 64.3% for homologous H1N1 seroconverters vs. 21.9% for non-seroconverters, p=0.001.

Conclusion:

This is the first study to show that transplant recipients were able to mount significant cross-reactive (i.e. heterologous) responses to influenza vaccine. Seroconversion to the heterologous strain was more likely if the patient had responded to the homologous vaccine strain. The adjuvanted vaccine group had similar heterologous responses to the nonadjuvanted vaccine.

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