Antibody and T-Cell Response to Bivalent Booster SARS-CoV-2 Vaccines in People With Compromised Immune Function: COVERALL-3 Study
Authors: Amstutz Alain , Chammartin Frédérique , Audigé Annette , Eichenberger Anna L , Braun Dominique L , Amico Patrizia , Stoeckle Marcel P , Hasse Barbara , Papadimitriou-Olivgeris Matthaios , Manuel Oriol , Bongard Cédric , Schuurmans Macé M , Hage René , Damm Dominik , Tamm Michael , Mueller Nicolas J , Rauch Andri , Günthard Huldrych F , Koller Michael T , Schönenberger Christof M , Griessbach Alexandra , Labhardt Niklaus D , Kouyos Roger D , Trkola Alexandra , Kusejko Katharina , Bucher Heiner C , Abela Irene A , Briel Matthias , Speich Benjamin ,   Swiss HIV Cohort Study, Abela I , Aebi-Popp K , Anagnostopoulos A , Battegay M , Bernasconi E , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Hachfeld A , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Jackson-Perry D , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Kusejko K , Labhardt N , Leuzinger K , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nemeth J , Nicca D , Notter J , Paioni P , Pantaleo G , Perreau M , Rauch A , Salazar-Vizcaya L , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Wandeler G , Weisser M , Yerly S ,   the Swiss Transplant Cohort, Amico Patrizia , Aubert John-David , Banz Vanessa , Beckmann Sonja , Beldi Guido , Berger Christoph , Berishvili Ekaterine , Berzigotti Annalisa , Binet Isabelle , Bochud Pierre-Yves , Branca Sanda , Bucher Heiner C , Catana Emmanuelle , Cairoli Anne , Chalandon Yves , De Geest Sabina , De Rougemont Olivier , De Seigneux Sophie , Dickenmann Michael , Dreifuss Joëlle Lynn , Duchosal Michel , Fehr Thomas , Ferrari-Lacraz Sylvie , Garzoni Christian , Golshayan Déla , Goossens Nicolas , Haidar Fadi , Halter Jörg , Heim Dominik , Hess Christoph , Hillinger Sven , Hirsch Hans H , Hirt Patricia , Hoessly Linard , Hofbauer Günther , Huynh-Do Uyen , Immer Franz , Koller Michael , Laesser Bettina , Lamoth Frédéric , Lehmann Roger , Leichtle Alexander , Manuel Oriol , Marti Hans-Peter , Martinelli Michele , McLin Valérie , Mellac Katell , Merçay Aurélia , Mettler Karin , Mueller Nicolas J , Müller-Arndt Ulrike , Müllhaupt Beat , Nägeli Mirjam , Oldani Graziano , Pascual Manuel , Passweg Jakob , Pazeller Rosemarie , Posfay-Barbe Klara , Rick Juliane , Rosselet Anne , Rossi Simona , Rothlin Silvia , Ruschitzka Frank , Schachtner Thomas , Schaub Stefan , Scherrer Alexandra , Schnyder Aurelia , Schuurmans Macé , Schwab Simon , Sengstag Thierry , Simonetta Federico , Stampf Susanne , Steiger Jürg , Stirnimann Guido , Stürzinger Ueli , Van Delden Christian , Venetz Jean-Pierre , Villard Jean , Vionnet Julien , Wick Madeleine , Wilhelm Markus , Yerly Patrick 
Published: June 2024

Abstract

Background
Bivalent messenger RNA (mRNA) vaccines, designed to combat emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination.

Methods
Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months postvaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/mL (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics.

Results
In SHCS participants, baseline anti-spike antibody concentrations ≥1642 units/mL were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642 units/mL, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a 5-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events.

Conclusions
Bivalent mRNA vaccination elicited a robust humoral response in individuals with human immunodeficiency virus (HIV) or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare.
Clinical Trials Registration . NCT04805125.