Immunosuppressed patients are at higher risks of influenza complications. This was evidenced by reports of disease outcome in solid organ transplant (SOT) recipients infected by the pandemic influenza A/09/H1N1 strain –. A similar risk exists in HIV infected individuals with advanced disease and low CD4 cell count but not in HAART-treated patients –.
Immunosuppressed patients have a general trend toward impaired antibody responses to non-adjuvanted vaccines . Short-term antibody responses were indeed lower following 1 or 2 doses of non-adjuvanted influenza A/09/H1N1 vaccines in HIV-infected ,  and solid organ transplant (SOT) patients –.
The extent to which adjuvanted vaccines may improve responses is thus of central interest. In HIV-infected patients, a single dose of the AS03-adjuvanted pandemic vaccine (Pandemrix®) elicited higher responses than non-adjuvanted monovalent vaccines . Four weeks after 1 dose of Pandemrix®, seroresponses remained lower than in controls ,  reaching similar titers after 2 doses –. Seroresponses remained lower in SOT recipients even after 2 doses of Pandemrix® , , , reflecting a more profound impact of immunosuppression on vaccine responses.
How immunosuppression affects memory responses is less well defined. In HIV-infected patients, impaired B and T cell functions cause dysfunctional germinal center interactions  and result in a progressive loss of B-cell memory despite antiretroviral therapy –. Accordingly, most HAART-treated HIV-infected adults reached a hemagglutination inhibition titer (HAI) ≥1/40 four weeks after immunization with non-adjuvanted A/09/H1N1 vaccines but only 28% remained above this threshold at 6 months . How the immunosuppression of SOT patients affects memory responses is less well described.
In 2009/2010, we had followed 760 immunocompromised and 133 healthy adults immunized with 1 (healthy) or 2 (patients) doses of Pandemrix®. Four weeks after immunization, we observed similar responses in HIV-infected individuals after 2 doses as in healthy adults after 1 dose , and lower seroresponses in SOT recipients despite 2 immunizations . To define how adjuvanted vaccines would influence antibody persistence and memory responses, we assessed the impact of 2009/2010 priming with Pandemrix® on antibody persistence and memory responses elicited in 2010/2011 by one dose of a non-adjuvanted trivalent inactivated seasonal vaccine including the same influenza A/09/H1N1 strain.
Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC).
Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons.
Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients.
Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients.