The multivariate regression correlation test between age, BMI, and CD4/CD8 ratio on neutralizing antibodies (NAbs) titer was preceded by the Shapiro-Wilk normality test
Shapiro-Wilk test
Age
BMI (kg/m2)
Ratio CD4/CD8
Vitamin D
NAb
Mean
47.02
23.86
1.29
14.47
37.33
Standard deviation
15.41
3.65
0.44
7.73
26.83
Asymptotic significance
0.058
0.200
0.182
0.034
0.068
Predictor
R
R square
P
Age, BMI, ratio CD4/CD8
0.441
0.195
0.033
Multiple correlation test
Coefficients
P
Constant
69.462
0.029
Age
0.225
0.371
BMI
–2.577
0.018
Ratio CD4/CD8
14.589
0.099
Declarations
Acknowledgments
We thank Prodia Clinical Laboratory for examining the blood samples.
Author contributions
HR: Conceptualization, Investigation, Data curation, Formal analysis, Methodology, Writing—original draft. FT, GP, and AAP: Writing—review & editing. SF: Data curation, Writing—review & editing. All authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
The studies involving human participants were reviewed and approved by the Ethics Committee of Immanuel Hospital, Bandung, Indonesia (ethics approval number: 36/A01/EC/IX/2021).
Consent to participate
Informed consent to participate in the study was obtained from all participants.
Consent to publication
Not applicable.
Availability of data and materials
The data presented in this study are available on request from the corresponding author.
Funding
This study was supported by the Universitas Kristen Maranatha, Bandung, Indonesia, under the B scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Li L, Guo P, Zhang X, Yu Z, Zhang W, Sun H. SARS-CoV-2 vaccine candidates in rapid development.Hum Vaccin Immunother. 2021;17:644–53. [DOI] [PubMed] [PMC]
Su F, Patel GB, Hu S, Chen W. Induction of mucosal immunity through systemic immunization: Phantom or reality?Hum Vaccin Immunother. 2016;12:1070–9. [DOI] [PubMed] [PMC]
Carsetti R, Quinti I. Editorial: IgA and mucosal immunity in vaccinology and in protection from infection.Front Cell Infect Microbiol. 2024;14:1409111. [DOI] [PubMed] [PMC]
Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses.Nat Microbiol. 2020;5:562–9. [DOI] [PubMed] [PMC]
Amanat F, Krammer F. SARS-CoV-2 Vaccines: Status Report.Immunity. 2020;52:583–9. [DOI] [PubMed] [PMC]
Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.J Virol. 2020;94:e02015–19. [DOI] [PubMed] [PMC]
Leitner WW, Haraway M, Pierson T, Bergmann-Leitner ES. Role of Opsonophagocytosis in Immune Protection against Malaria.Vaccines (Basel). 2020;8:264. [DOI] [PubMed] [PMC]
Terpos E, Karalis V, Ntanasis-Stathopoulos I, Evangelakou Z, Gavriatopoulou M, Manola MS, et al. Comparison of Neutralizing Antibody Responses at 6 Months Post Vaccination with BNT162b2 and AZD1222.Biomedicines. 2022;10:338. [DOI] [PubMed] [PMC]
Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.Nat Med. 2021;27:1205–11. [DOI] [PubMed]
Yu J, Tostanoski LH, Peter L, Mercado NB, McMahan K, Mahrokhian SH, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques.Science. 2020;369:806–11. [DOI] [PubMed] [PMC]
Wajnberg A, Amanat F, Firpo A, Altman DR, Bailey MJ, Mansour M, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months.Science. 2020;370:1227–30. [DOI] [PubMed] [PMC]
Iyer AS, Jones FK, Nodoushani A, Kelly M, Becker M, Slater D, et al. Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.Sci Immunol. 2020;5:eabe0367. [DOI] [PubMed] [PMC]
Popkin BM, Du S, Green WD, Beck MA, Algaith T, Herbst CH, et al. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships.Obes Rev. 2020;21:e13128. [DOI] [PubMed] [PMC]
Martínez-Colón GJ, Ratnasiri K, Chen H, Jiang S, Zanley E, Rustagi A, et al. SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages.Sci Transl Med. 2022;14:eabm9151. [DOI] [PubMed] [PMC]
Luckheeram RV, Zhou R, Verma AD, Xia B. CD4⁺T cells: differentiation and functions.Clin Dev Immunol. 2012;2012:925135. [DOI] [PubMed] [PMC]
McBride JA, Striker R. Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health?PLoS Pathog. 2017;13:e1006624. [DOI] [PubMed] [PMC]
Wørzner K, Sheward DJ, Schmidt ST, Hanke L, Zimmermann J, McInerney G, et al. Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice.EBioMedicine. 2021;63:103197. [DOI] [PubMed] [PMC]
Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K. Causes, consequences, and reversal of immune system aging.J Clin Invest. 2013;123:958–65. [DOI] [PubMed] [PMC]
Lalor MK, Floyd S, Gorak-Stolinska P, Weir RE, Blitz R, Branson K, et al. BCG vaccination: a role for vitamin D?PLoS One. 2011;6:e16709. [DOI] [PubMed] [PMC]
Zitt E, Sprenger-Mähr H, Knoll F, Neyer U, Lhotta K. Vitamin D deficiency is associated with poor response to active hepatitis B immunisation in patients with chronic kidney disease.Vaccine. 2012;30:931–5. [DOI] [PubMed]
Ho JQ, Sepand MR, Bigdelou B, Shekarian T, Esfandyarpour R, Chauhan P, et al. The immune response to COVID-19: Does sex matter?Immunology. 2022;166:429–43. [DOI] [PubMed] [PMC]
Lamas O, Marti A, Martínez JA. Obesity and immunocompetence.Eur J Clin Nutr. 2002;56:S42–5. [DOI] [PubMed]
Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.Aging Clin Exp Res. 2020;32:1195–8. [DOI] [PubMed] [PMC]
Frasca D, Ferracci F, Diaz A, Romero M, Lechner S, Blomberg BB. Obesity decreases B cell responses in young and elderly individuals.Obesity (Silver Spring). 2016;24:615–25. [DOI] [PubMed] [PMC]
Martí A, Marcos A, Martínez JA. Obesity and immune function relationships.Obes Rev. 2001;2:131–40. [DOI] [PubMed]
Liu D, Yuan X, Gao F, Zhao B, Ding L, Huan M, et al. High Number and Specific Comorbidities Could Impact the Immune Response in COVID-19 Patients.Front Immunol. 2022;13:899930. [DOI] [PubMed] [PMC]
Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Löfgren S, et al. An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans.J Gerontol A Biol Sci Med Sci. 2005;60:556–65. [DOI] [PubMed]
Pawelec G, Derhovanessian E. Role of CMV in immune senescence.Virus Res. 2011;157:175–9. [DOI] [PubMed]
Boraschi D, Del Giudice G, Dutel C, Ivanoff B, Rappuoli R, Grubeck-Loebenstein B. Ageing and immunity: addressing immune senescence to ensure healthy ageing.Vaccine. 2010;28:3627–31. [DOI] [PubMed]
Guo L, Wang Y, Kang L, Hu Y, Wang L, Zhong J, et al. Cross-reactive antibody against human coronavirus OC43 spike protein correlates with disease severity in COVID-19 patients: a retrospective study.Emerg Microbes Infect. 2021;10:664–76. [DOI] [PubMed] [PMC]
Sealy RE, Hurwitz JL. Cross-Reactive Immune Responses toward the Common Cold Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Mini-Review and a Murine Study.Microorganisms. 2021;9:1643. [DOI] [PubMed] [PMC]
Wagner A, Weinberger B. Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives.Front Immunol. 2020;11:717. [DOI] [PubMed] [PMC]
Fish EN. The X-files in immunity: sex-based differences predispose immune responses.Nat Rev Immunol. 2008;8:737–44. [DOI] [PubMed] [PMC]
Wikby A, Månsson IA, Johansson B, Strindhall J, Nilsson SE. The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age.Biogerontology. 2008;9:299–308. [DOI] [PubMed]
Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiébaut R, et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination.Proc Natl Acad Sci U S A. 2014;111:869–74. [DOI] [PubMed] [PMC]
Engler RJM, Nelson MR, Klote MM, VanRaden MJ, Huang C, Cox NJ, et al. Half- vs full-dose trivalent inactivated influenza vaccine (2004-2005): age, dose, and sex effects on immune responses.Arch Intern Med. 2008;168:2405–14. [DOI] [PubMed]
Ciabattini A, Nardini C, Santoro F, Garagnani P, Franceschi C, Medaglini D. Vaccination in the elderly: The challenge of immune changes with aging.Semin Immunol. 2018;40:83–94. [DOI] [PubMed]
Tartof SY, Qian L, Hong V, Wei R, Nadjafi RF, Fischer H, et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization.Ann Intern Med. 2020;173:773–81. [DOI] [PubMed] [PMC]
Francisco V, Pino J, Campos-Cabaleiro V, Ruiz-Fernández C, Mera A, Gonzalez-Gay MA, et al. Obesity, Fat Mass and Immune System: Role for Leptin.Front Physiol. 2018;9:640. [DOI] [PubMed] [PMC]
Frasca D, Blomberg BB. Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging.Front Immunol. 2017;8:1003. [DOI] [PubMed] [PMC]
Kiernan K, MacIver NJ. The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease.Front Immunol. 2021;11:622468. [DOI] [PubMed] [PMC]
de Heredia FP, Gómez-Martínez S, Marcos A. Obesity, inflammation and the immune system.Proc Nutr Soc. 2012;71:332–8. [DOI] [PubMed]
Sheridan PA, Paich HA, Handy J, Karlsson EA, Hudgens MG, Sammon AB, et al. Obesity is associated with impaired immune response to influenza vaccination in humans.Int J Obes (Lond). 2012;36:1072–7. [DOI] [PubMed] [PMC]
Butsch WS, Hajduk A, Cardel MI, Donahoo WT, Kyle TK, Stanford FC, et al. COVID-19 vaccines are effective in people with obesity: A position statement from The Obesity Society.Obesity (Silver Spring). 2021;29:1575–9. [DOI] [PubMed] [PMC]
Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, et al. Comorbidity and its Impact on Patients with COVID-19.SN Compr Clin Med. 2020;2:1069–76. [DOI] [PubMed] [PMC]
Xia C, Rao X, Zhong J. Role of T Lymphocytes in Type 2 Diabetes and Diabetes-Associated Inflammation.J Diabetes Res. 2017;2017:6494795. [DOI] [PubMed] [PMC]
Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A. Human immunosenescence: is it infectious?Immunol Rev. 2005;205:257–68. [DOI] [PubMed]
Fantini C, Corinaldesi C, Lenzi A, Migliaccio S, Crescioli C. Vitamin D as a Shield against Aging.Int J Mol Sci. 2023;24:4546. [DOI] [PubMed] [PMC]
Singh S, Kaur R, Singh RK. Revisiting the role of vitamin D levels in the prevention of COVID-19 infection and mortality in European countries post infections peak.Aging Clin Exp Res. 2020;32:1609–12. [DOI] [PubMed] [PMC]
Piec I, Cook L, Dervisevic S, Fraser WD, Ruetten S, Berman M, et al. Age and vitamin D affect the magnitude of the antibody response to the first dose of the SARS-CoV-2 BNT162b2 vaccine.Curr Res Transl Med. 2022;70:103344. [DOI] [PubMed] [PMC]
Sadarangani SP, Whitaker JA, Poland GA. “Let there be light”: the role of vitamin D in the immune response to vaccines.Expert Rev Vaccines. 2015;14:1427–40. [DOI] [PubMed] [PMC]
Heine G, Drozdenko G, Lahl A, Unterwalder N, Mei H, Volk H, et al. Efficient tetanus toxoid immunization on vitamin D supplementation.Eur J Clin Nutr. 2011;65:329–34. [DOI] [PubMed]
