Siegrist C-A, Aspinall R. B-cell responses to vaccination at the extremes of age. Nat Rev Immunol. 2009;9(3):185–94.

Article  CAS  PubMed  Google Scholar 

Ma S, Wang C, Mao X, Hao Y. B cell dysfunction associated with aging and autoimmune diseases. Front Immunol. 2019;10.

Haynes L, Eaton SM, Burns EM, Randall TD, Swain SL. CD4 T cell memory derived from young Naive cells functions well into old age, but memory generated from aged Naive cells functions poorly. Proc Natl Acad Sci U S A. 2003;100(25):15053–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ratliff M, Alter S, Frasca D, Blomberg BB, Riley RL. In senescence, age-associated B cells secrete TNFα and inhibit survival of B-cell precursors*. Aging Cell. 2013;12(2):303–11.

Article  CAS  PubMed  Google Scholar 

Frasca D, Blomberg BB. Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination. Immun Ageing. 2020;17(1):37.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hao Y, O’Neill P, Naradikian MS, Scholz JL, Cancro MP. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood. 2011;118(5):1294–304.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gibson KL, Wu YC, Barnett Y, Duggan O, Vaughan R, Kondeatis E, et al. B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell. 2009;8(1):18–25.

Article  CAS  PubMed  Google Scholar 

Weinberger B, Herndler-Brandstetter D, Schwanninger A, Weiskopf D, Grubeck-Loebenstein B. Biology of immune responses to vaccines in elderly persons. Clin Infect Diseases: Official Publication Infect Dis Soc Am. 2008;46(7):1078–84.

Article  Google Scholar 

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15.

Article  CAS  PubMed  Google Scholar 

Cunningham AL, McIntyre P, Subbarao K, Booy R, Levin MJ. Vaccines for older adults. BMJ (Clinical Res ed). 2021;372:n188.

Google Scholar 

Collier DA, Ferreira IATM, Kotagiri P, Datir RP, Lim EY, Touizer E, et al. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature. 2021;596(7872):417–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jergović M, Uhrlaub JL, Watanabe M, Bradshaw CM, White LM, LaFleur BJ, et al. Competent immune responses to SARS-CoV-2 variants in older adults following two doses of mRNA vaccination. Nat Commun. 2022;13(1):2891.

Article  PubMed  PubMed Central  Google Scholar 

Renia L, Goh YS, Rouers A, Le Bert N, Chia WN, Chavatte J-M, et al. Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose. Nat Commun. 2022;13(1):4615.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Romero-Olmedo AJ, Schulz AR, Hochstätter S, Das Gupta D, Virta I, Hirseland H, et al. Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults. Nat Microbiol. 2022;7(2):195–9.

Article  CAS  PubMed  Google Scholar 

Sasson JM, Campo JJ, Carpenter RM, Young MK, Randall AZ, Trappl-Kimmons K, et al. Diverse humoral immune responses in younger and older adult COVID-19 patients. mBio. 2021;12(3). https://doi.org/10.1128/mbio.01229-21.

Bartleson JM, Radenkovic D, Covarrubias AJ, Furman D, Winer DA, Verdin E. SARS-CoV-2, COVID-19 and the ageing immune system. Nat Aging. 2021;1(9):769–82.

Article  PubMed  PubMed Central  Google Scholar 

Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: what we May expect regarding pathogenesis, immune responses, and outcomes. GeroScience. 2020;42(2):505–14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383(25):2427–38.

Article  CAS  PubMed  Google Scholar 

Liang X-M, Xu Q-Y, Jia Z-J, Wu M-J, Liu Y-Y, Lin L-R et al. A third dose of an inactivated vaccine dramatically increased the levels and decay times of Anti-SARS-CoV-2 antibodies, but disappointingly declined again: A prospective, longitudinal, cohort study at 18 serial time points over 368 days. Front Immunol. 2022;13.

Semelka CT, DeWitt ME, Blevins MW, Holbrook BC, Sanders JW, Alexander-Miller MA. Frailty impacts immune responses to moderna COVID-19 mRNA vaccine in older adults. Immun Ageing: I A. 2023;20(1):4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu K, Wang Z, Qin M, Gao Y, Luo N, Xie W, et al. A systematic review and meta-analysis of the effectiveness and safety of COVID-19 vaccination in older adults. Front Immunol. 2023;14:1113156.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Castaldello A, Brocca-Cofano E, Voltan R, Triulzi C, Altavilla G, Laus M, et al. DNA prime and protein boost immunization with innovative polymeric cationic core-shell nanoparticles elicits broad immune responses and strongly enhance cellular responses of HIV-1 Tat DNA vaccination. Vaccine. 2006;24(29):5655–69.

Article  CAS  PubMed  Google Scholar 

Wang S, Kennedy JS, West K, Montefiori DC, Coley S, Lawrence J, et al. Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers. Vaccine. 2008;26(31):3947–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vaine M, Wang S, Hackett A, Arthos J, Lu S. Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity. Vaccine. 2010;28(17):2999–3007.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Menon V, Ayala VI, Rangaswamy SP, Kalisz I, Whitney S, Galmin L, et al. DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric Simian immunodeficiency virus envelope and advax delta inulin adjuvant. J Gen Virol. 2017;98(8):2143–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li H, Wang S, Hu G, Zhang L, Liu S, Lu S. DNA priming immunization is more effective than Recombinant protein vaccine in eliciting antigen-specific B cell responses. Emerg Microbes Infections. 2021;10(1):833–41.

Article  CAS  Google Scholar 

Pflumm D, Seidel A, Klein F, Groß R, Krutzke L, Kochanek S, et al. Heterologous DNA-prime/protein-boost immunization with a monomeric SARS-CoV-2 Spike antigen redundantizes the trimeric receptor-binding domain structure to induce neutralizing antibodies in old mice. Front Immunol. 2023;14:1231274.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leins H, Mulaw M, Eiwen K, Sakk V, Liang Y, Denkinger M, et al. Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood. 2018;132(6):565–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hale JS, Boursalian TE, Turk GL, Fink PJ. Thymic output in aged mice. Proc Natl Acad Sci U S A. 2006;103(22):8447–52.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Becklund BR, Purton JF, Ramsey C, Favre S, Vogt TK, Martin CE, et al. The aged lymphoid tissue environment fails to support Naïve T cell homeostasis. Sci Rep. 2016;6:30842.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev. 2014;259(1):88–102.

Article  CAS  PubMed