Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine

Claire-Anne Siegrist, Christian van Delden, Michael Bel, Christophe Combescure, Cécile Delhumeau, Matthias Cavassini, Olivier Clerc, Sara Meier, Karine Hadaya, Paola M Soccal, Sabine Yerly, Laurent Kaiser, Bernard Hirschel, Alexandra Calmy, H1N1 Study Group, Swiss HIV Cohort Study (SHCS), C A Siegrist, K Posfay-Barbe, S Meier, M Bel, S Grillet, G Sealy, J Demeules, S Charvat, M Verdon, C Combescure, B Hirschel, A Calmy, C Delhumeau-Cartier, C Gabay, P A Guerne, J Seebach, C Ribi, J Villard, P Y Dietrich, A C George, L Favet, C van Delden, I Morard, G Mentha, E Giostra, K Hadaya, P Y Martin, P Soccal, T Berney, S Noble, B Mohty, M Nagy, Y Chalandon, E Roosnek, J Passweg, L Kaiser, S Yerly, Y Thomas, W Wunderli, J Barth, M Battegay, E Bernasconi, J Böni, H C Bucher, C Burton-Jeangros, A Calmy, M Cavassini, C Cellerai, M Egger, L Elzi, J Fehr, J Fellay, M Flepp, P Francioli, H Furrer, C A Fux, M Gorgievski, H Günthard, D Haerry, B Hasse, H H Hirsch, B Hirschel, I Hösli, C Kahlert, L Kaiser, O Keiser, C Kind, T Klimkait, H Kovari, B Ledergerber, G Martinetti, B Martinez de Tejada, K Metzner, N Müller, D Nadal, G Pantaleo, A Rauch, S Regenass, M Rickenbach, C Rudin, P Schmid, D Schultze, F Schöni-Affolter, J Schüpbach, R Speck, P Taffé, P Tarr, A Telenti, A Trkola, P Vernazza, R Weber, S Yerly, Claire-Anne Siegrist, Christian van Delden, Michael Bel, Christophe Combescure, Cécile Delhumeau, Matthias Cavassini, Olivier Clerc, Sara Meier, Karine Hadaya, Paola M Soccal, Sabine Yerly, Laurent Kaiser, Bernard Hirschel, Alexandra Calmy, H1N1 Study Group, Swiss HIV Cohort Study (SHCS), C A Siegrist, K Posfay-Barbe, S Meier, M Bel, S Grillet, G Sealy, J Demeules, S Charvat, M Verdon, C Combescure, B Hirschel, A Calmy, C Delhumeau-Cartier, C Gabay, P A Guerne, J Seebach, C Ribi, J Villard, P Y Dietrich, A C George, L Favet, C van Delden, I Morard, G Mentha, E Giostra, K Hadaya, P Y Martin, P Soccal, T Berney, S Noble, B Mohty, M Nagy, Y Chalandon, E Roosnek, J Passweg, L Kaiser, S Yerly, Y Thomas, W Wunderli, J Barth, M Battegay, E Bernasconi, J Böni, H C Bucher, C Burton-Jeangros, A Calmy, M Cavassini, C Cellerai, M Egger, L Elzi, J Fehr, J Fellay, M Flepp, P Francioli, H Furrer, C A Fux, M Gorgievski, H Günthard, D Haerry, B Hasse, H H Hirsch, B Hirschel, I Hösli, C Kahlert, L Kaiser, O Keiser, C Kind, T Klimkait, H Kovari, B Ledergerber, G Martinetti, B Martinez de Tejada, K Metzner, N Müller, D Nadal, G Pantaleo, A Rauch, S Regenass, M Rickenbach, C Rudin, P Schmid, D Schultze, F Schöni-Affolter, J Schüpbach, R Speck, P Taffé, P Tarr, A Telenti, A Trkola, P Vernazza, R Weber, S Yerly

Abstract

Background: 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).

Method: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT01022905.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Distribution and kinetics of antibody…
Figure 1. Distribution and kinetics of antibody titers.
A–C. Blood was collected before and 4 weeks after 1 dose of non-adjuvanted 2010/2011 seasonal influenza vaccine. Antibody titers were assessed by hemagglutination inhibition (HAI). The results were expressed as the reciprocal of the highest dilution showing a positive HAI (see Methods). The vertical dotted line represents the seroprotection threshold (titer 1∶40). The curves represent the distribution of individual antibody titers in each group. D-F: Geometric mean HAI titers to influenza A/09/H1N1 (D, E) and A/09/H3N2 (F) were measured before (pre-2009) and after (post-2009) immunization with 1 (controls) or 2 (patients) doses of AS03-adjuvanted pandemic vaccine, and before (pre-2010) and after (post-2010) 1 dose of non-adjuvanted 2010/2011 seasonal influenza vaccine. D: All patients followed in 2010/2011. E -F: Patients followed for 2 consecutive seasons.

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Source: PubMed

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