Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH
Abstract
:1. Introduction
2. Results
2.1. Demographic and Clinical Characteristics of PLWH
2.2. Evaluation of Spike-Specific Humoral and T-Cell Response in Study Population
2.3. Evaluation of Spike-Specific Humoral and T-Cell Response in PLWH Stratified According to CD4 Cell Count
2.4. Evaluation of Spike-Specific Humoral and T-Cell Response in PLWH Stratified According to Humoral Response
2.5. Correlations between Current CD4 Cell Count and T-Cell Response
2.6. Evaluation of Spike-Specific Humoral and T-Cell at T2 in PLWH
3. Discussion
4. Materials and Methods
4.1. Study Design and Participants
4.2. Evaluation of Anti-S Antibodies
4.3. Determination of Anti-N Antibodies
4.4. T-Cell Stimulation with SARS-CoV-2–Specific Peptide Libraries
4.5. Flow Cytometry Assay of Stimulated T-Cells
4.6. Ethics Statement
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727–733. [Google Scholar] [CrossRef] [PubMed]
- Governo Italiano. Report Vaccini Anti Covid-19. Available online: https://www.governo.it/it/cscovid19/report-vaccini/ (accessed on 8 March 2022).
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef] [PubMed]
- Sahin, U.; Muik, A.; Derhovanessian, E.; Vogler, I.; Kranz, L.M.; Vormehr, M.; Baum, A.; Pascal, K.; Quandt, J.; Maurus, D.; et al. COVID-19 Vaccine BNT162b1 Elicits Human Antibody and TH1 T Cell Responses. Nature 2020, 586, 594–599. [Google Scholar] [CrossRef]
- Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the MRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef] [PubMed]
- Kalimuddin, S.; Tham, C.Y.L.; Qui, M.; de Alwis, R.; Sim, J.X.Y.; Lim, J.M.E.; Tan, H.-C.; Syenina, A.; Zhang, S.L.; Le Bert, N.; et al. Early T Cell and Binding Antibody Responses Are Associated with COVID-19 RNA Vaccine Efficacy Onset. Medicine 2021, 2, 682–688.e4. [Google Scholar] [CrossRef]
- Turner, J.S.; Kim, W.; Kalaidina, E.; Goss, C.W.; Rauseo, A.M.; Schmitz, A.J.; Hansen, L.; Haile, A.; Klebert, M.K.; Pusic, I.; et al. SARS-CoV-2 Infection Induces Long-Lived Bone Marrow Plasma Cells in Humans. Nature 2021, 595, 421–425. [Google Scholar] [CrossRef] [PubMed]
- Altmann, D.M.; Boyton, R.J.; Beale, R. Immunity to SARS-CoV-2 Variants of Concern. Science 2021, 371, 1103–1104. [Google Scholar] [CrossRef]
- Tarke, A.; Sidney, J.; Methot, N.; Yu, E.D.; Zhang, Y.; Dan, J.M.; Goodwin, B.; Rubiro, P.; Sutherland, A.; Wang, E.; et al. Impact of SARS-CoV-2 Variants on the Total CD4+ and CD8+ T Cell Reactivity in Infected or Vaccinated Individuals. Cell Rep. Med. 2021, 2, 100355. [Google Scholar] [CrossRef] [PubMed]
- Woldemeskel, B.A.; Garliss, C.C.; Blankson, J.N. SARS-CoV-2 MRNA Vaccines Induce Broad CD4+ T Cell Responses That Recognize SARS-CoV-2 Variants and HCoV-NL63. J. Clin. Investig. 2021, 131, e149335. [Google Scholar] [CrossRef] [PubMed]
- Hoffmann, C.; Casado, J.L.; Härter, G.; Vizcarra, P.; Moreno, A.; Cattaneo, D.; Meraviglia, P.; Spinner, C.D.; Schabaz, F.; Grunwald, S.; et al. Immune Deficiency Is a Risk Factor for Severe COVID-19 in People Living with HIV. HIV Med. 2021, 22, 372–378. [Google Scholar] [CrossRef] [PubMed]
- Alrubayyi, A.; Gea-Mallorquí, E.; Touizer, E.; Hameiri-Bowen, D.; Kopycinski, J.; Charlton, B.; Fisher-Pearson, N.; Muir, L.; Rosa, A.; Roustan, C.; et al. Characterization of Humoral and SARS-CoV-2 Specific T Cell Responses in People Living with HIV. Nat. Commun. 2021, 12, 5839. [Google Scholar] [CrossRef] [PubMed]
- Rydyznski Moderbacher, C.; Ramirez, S.I.; Dan, J.M.; Grifoni, A.; Hastie, K.M.; Weiskopf, D.; Belanger, S.; Abbott, R.K.; Kim, C.; Choi, J.; et al. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell 2020, 183, 996–1012.e19. [Google Scholar] [CrossRef]
- Tebas, P.; Frank, I.; Lewis, M.; Quinn, J.; Zifchak, L.; Thomas, A.; Kenney, T.; Kappes, R.; Wagner, W.; Maffei, K.; et al. Poor Immunogenicity of the H1N1 2009 Vaccine in Well Controlled HIV-Infected Individuals. AIDS 2010, 24, 2187–2192. [Google Scholar] [CrossRef]
- Muema, D.M.; Macharia, G.N.; Hassan, A.S.; Mwaringa, S.M.; Fegan, G.W.; Berkley, J.A.; Nduati, E.W.; Urban, B.C. Control of Viremia Enables Acquisition of Resting Memory B Cells with Age and Normalization of Activated B Cell Phenotypes in HIV-Infected Children. J. Immunol. 2015, 195, 1082–1091. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guaraldi, G.; Orlando, G.; Zona, S.; Menozzi, M.; Carli, F.; Garlassi, E.; Berti, A.; Rossi, E.; Roverato, A.; Palella, F. Premature Age-Related Comorbidities among HIV-Infected Persons Compared with the General Population. Clin. Infect. Dis. 2011, 53, 1120–1126. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Woldemeskel, B.A.; Karaba, A.H.; Garliss, C.C.; Beck, E.J.; Wang, K.H.; Laeyendecker, O.; Cox, A.L.; Blankson, J.N. The BNT162b2 MRNA Vaccine Elicits Robust Humoral and Cellular Immune Responses in People Living With Human Immunodeficiency Virus (HIV). Clin. Infect. Dis. 2021, 74, ciab648. [Google Scholar] [CrossRef]
- Levy, I.; Wieder-Finesod, A.; Litchevsky, V.; Biber, A.; Indenbaum, V.; Olmer, L.; Huppert, A.; Mor, O.; Goldstein, M.; Levin, E.G.; et al. Immunogenicity and Safety of the BNT162b2 MRNA COVID-19 Vaccine in People Living with HIV-1. Clin. Microbiol. Infect. 2021, 27, 1851–1855. [Google Scholar] [CrossRef] [PubMed]
- Ruddy, J.A.; Boyarsky, B.J.; Bailey, J.R.; Karaba, A.H.; Garonzik-Wang, J.M.; Segev, D.L.; Durand, C.M.; Werbel, W.A. Safety and Antibody Response to Two-Dose SARS-CoV-2 Messenger RNA Vaccination in Persons with HIV. AIDS 2021, 35, 2399–2401. [Google Scholar] [CrossRef]
- Lombardi, A.; Butta, G.M.; Donnici, L.; Bozzi, G.; Oggioni, M.; Bono, P.; Matera, M.; Consonni, D.; Ludovisi, S.; Muscatello, A.; et al. Anti-Spike Antibodies and Neutralising Antibody Activity in People Living with HIV Vaccinated with COVID-19 MRNA-1273 Vaccine: A Prospective Single-Centre Cohort Study. Lancet Reg. Health Eur. 2022, 13, 100287. [Google Scholar] [CrossRef] [PubMed]
- Antinori, A.; Cicalini, S.; Meschi, S.; Bordoni, V.; Lorenzini, P.; Vergori, A.; Lanini, S.; De Pascale, L.; Matusali, G.; Mariotti, D.; et al. Humoral and Cellular Immune Response Elicited by MRNA Vaccination against SARS-CoV-2 in People Living with HIV (PLWH) Receiving Antiretroviral Therapy (ART) According with Current CD4 T-Lymphocyte Count. Clin. Infect. Dis. 2022, 75, ciac238. [Google Scholar] [CrossRef]
- Seder, R.A.; Darrah, P.A.; Roederer, M. T-Cell Quality in Memory and Protection: Implications for Vaccine Design. Nat. Rev. Immunol. 2008, 8, 247–258. [Google Scholar] [CrossRef] [PubMed]
- Bertoletti, A.; Le Bert, N.; Qui, M.; Tan, A.T. SARS-CoV-2-Specific T Cells in Infection and Vaccination. Cell. Mol. Immunol. 2021, 18, 2307–2312. [Google Scholar] [CrossRef] [PubMed]
- Betts, M.R.; Nason, M.C.; West, S.M.; De Rosa, S.C.; Migueles, S.A.; Abraham, J.; Lederman, M.M.; Benito, J.M.; Goepfert, P.A.; Connors, M.; et al. HIV Nonprogressors Preferentially Maintain Highly Functional HIV-Specific CD8+ T Cells. Blood 2006, 107, 4781–4789. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Painter, M.M.; Mathew, D.; Goel, R.R.; Apostolidis, S.A.; Pattekar, A.; Kuthuru, O.; Baxter, A.E.; Herati, R.S.; Oldridge, D.A.; Gouma, S.; et al. Rapid Induction of Antigen-Specific CD4+ T Cells Is Associated with Coordinated Humoral and Cellular Immunity to SARS-CoV-2 MRNA Vaccination. Immunity 2021, 54, 2133–2142.e3. [Google Scholar] [CrossRef]
- Arunachalam, P.S.; Scott, M.K.D.; Hagan, T.; Li, C.; Feng, Y.; Wimmers, F.; Grigoryan, L.; Trisal, M.; Edara, V.V.; Lai, L.; et al. Systems Vaccinology of the BNT162b2 MRNA Vaccine in Humans. Nature 2021, 596, 410–416. [Google Scholar] [CrossRef]
- McElhaney, J.E.; Gravenstein, S.; Upshaw, C.M.; Hooton, J.W.; Krause, P.; Drinka, P. Immune Response to Influenza Vaccination in Institutionalized Elderly: Effect on Different T-Cell Subsets. Vaccine 1998, 16, 403–409. [Google Scholar] [CrossRef]
- Riou, C.; du Bruyn, E.; Stek, C.; Daroowala, R.; Goliath, R.T.; Abrahams, F.; Said-Hartley, Q.; Allwood, B.W.; Hsiao, N.-Y.; Wilkinson, K.A.; et al. Relationship of SARS-CoV-2-Specific CD4 Response to COVID-19 Severity and Impact of HIV-1 and Tuberculosis Coinfection. J. Clin. Investig. 2021, 131, 149125. [Google Scholar] [CrossRef]
- Schub, D.; Klemis, V.; Schneitler, S.; Mihm, J.; Lepper, P.M.; Wilkens, H.; Bals, R.; Eichler, H.; Gärtner, B.C.; Becker, S.L.; et al. High Levels of SARS-CoV-2-Specific T Cells with Restricted Functionality in Severe Courses of COVID-19. JCI Insight 2020, 5, 142167. [Google Scholar] [CrossRef]
- Feikin, D.R.; Higdon, M.M.; Abu-Raddad, L.J.; Andrews, N.; Araos, R.; Goldberg, Y.; Groome, M.J.; Huppert, A.; O’Brien, K.L.; Smith, P.G.; et al. Duration of Effectiveness of Vaccines against SARS-CoV-2 Infection and COVID-19 Disease: Results of a Systematic Review and Meta-Regression. Lancet 2022, 399, 924–944. [Google Scholar] [CrossRef] [PubMed]
- Darrah, P.A.; Patel, D.T.; De Luca, P.M.; Lindsay, R.W.B.; Davey, D.F.; Flynn, B.J.; Hoff, S.T.; Andersen, P.; Reed, S.G.; Morris, S.L.; et al. Multifunctional TH1 Cells Define a Correlate of Vaccine-Mediated Protection against Leishmania Major. Nat. Med. 2007, 13, 843–850. [Google Scholar] [CrossRef]
- Zingaropoli, M.A.; Iannetta, M.; Pontecorvo, S.; Anzivino, E.; Prezioso, C.; Rodio, D.M.; Morreale, M.; D’Abramo, A.; Oliva, A.; Lichtner, M.; et al. JC Virus-DNA Detection Is Associated with CD8 Effector Accumulation in Peripheral Blood of Patients with Multiple Sclerosis under Natalizumab Treatment, Independently from JC Virus Serostatus. Available online: https://www.hindawi.com/journals/bmri/2018/5297980/cta/ (accessed on 22 March 2018).
- Iannetta, M.; Landi, D.; Cola, G.; Campogiani, L.; Malagnino, V.; Teti, E.; Coppola, L.; Di Lorenzo, A.; Fraboni, D.; Buccisano, F.; et al. B-and T-Cell Responses After SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Receiving Disease Modifying Therapies: Immunological Patterns and Clinical Implications. Front. Immunol. 2021, 12, 796482. [Google Scholar] [CrossRef] [PubMed]
- Guardiani, M.; Zingaropoli, M.A.; Cogliati Dezza, F.; Centofanti, A.; Carillo, C.; Tortellini, E.; Dominelli, F.; Napoli, A.; Del Borgo, C.; Gaeta, A.; et al. Evaluation of Immunogenicity to Three Doses of the SARS-CoV-2 BNT162b2 MRNA Vaccine in Lung Transplant Patients. Vaccines 2022, 10, 1642. [Google Scholar] [CrossRef] [PubMed]
PLWH (n = 37) | HD (n = 18) | |
---|---|---|
Age, median (IQR) years | 61 (48–68) | 30 (30–53) |
Male/Female | 26/11 | 13/5 |
Current CD4 cell count (cells/µL) | 547 (308–714) | |
CD4+ cell count nadir, (cells/µL) | 90 (22–281) | |
HIV-RNA zenith (cp/mL) | 92,280 (17,000–544,323) | |
HIV-RNA (cp/mL) | 40 (40–166) | |
ART | ||
Dual (%) | 8/37 (22%) | |
Non-Dual (%) | 29/37 (78%) | |
Comorbidities | ||
Any (%) | 11/37 (30%) | |
More than one (%) | 26/37 (70%) | |
HCV serostatus | ||
Anti-HCV Ab positive (%) | 9/37 (24%) | |
Smoke status | ||
No (%) | 24/37 (65%) | |
Yes (%) | 13/37 (35%) |
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Tortellini, E.; Zingaropoli, M.A.; Mancarella, G.; Marocco, R.; Carraro, A.; Jamhour, M.; Barbato, C.; Guardiani, M.; Dominelli, F.; Pasculli, P.; et al. Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH. Int. J. Mol. Sci. 2022, 23, 14988. https://doi.org/10.3390/ijms232314988
Tortellini E, Zingaropoli MA, Mancarella G, Marocco R, Carraro A, Jamhour M, Barbato C, Guardiani M, Dominelli F, Pasculli P, et al. Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH. International Journal of Molecular Sciences. 2022; 23(23):14988. https://doi.org/10.3390/ijms232314988
Chicago/Turabian StyleTortellini, Eeva, Maria Antonella Zingaropoli, Giulia Mancarella, Raffaella Marocco, Anna Carraro, Meriem Jamhour, Christian Barbato, Mariasilvia Guardiani, Federica Dominelli, Patrizia Pasculli, and et al. 2022. "Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH" International Journal of Molecular Sciences 23, no. 23: 14988. https://doi.org/10.3390/ijms232314988