Skip to content
2000
image of Integration of Preclinical and Clinical Vaccine Safety and Immunogenicity Testing for Development of a Pediatric HIV Vaccine to Achieve Protective HIV Immunity Prior to Adolescence

Abstract

An optimal HIV vaccine should provide protective immunity before sexual debut to prevent infection in adolescents and young adults, including acute infections in women of childbearing age. Such a vaccine will likely require multiple sequential immunization doses and would therefore be ideally initiated in childhood. Many of the world’s most successful vaccines are initiated in childhood for the induction of lifelong immunity and/or immunity that can be boosted later in life as part of the WHO Expanded Program on Immunization (EPI). Thus, the EPI vaccine framework provides an infrastructure that could be leveraged for the implementation of a multidose HIV immunization regimen. Early childhood also provides a window of time in which there is minimal HIV exposure risk, and the plasticity of the early life immune landscape may present advantages for the elicitation of broadly neutralizing Antibodies (bnAbs), a primary target for HIV vaccination. Sequential vaccination with adjuvanted immunogens targeting specific bnAb lineages is a promising HIV vaccine strategy, and several vaccine candidates are currently being tested in adult clinical trials. It will be critical to evaluate the most promising immunogens and adjuvants in pediatric settings. Preclinical studies, including and modelling as well as studies in animal models, will be essential to guide the design of future pediatric vaccine trials. This review summarizes current advances in bnAb germline targeting immunization. It provides the rationale for a better integration of preclinical and clinical vaccine studies to facilitate the development of a vaccine that achieves protective immunity in preadolescence.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/chr/10.2174/011570162X366522250721113420
2025-08-08
2025-12-05
Loading full text...

Full text loading...

/deliver/fulltext/chr/10.2174/011570162X366522250721113420/BMS-CHIVR-2024-HT10-6091-14.html?itemId=/content/journals/chr/10.2174/011570162X366522250721113420&mimeType=html&fmt=ahah

References

  1. 2024 global AIDS report — The urgency of now: AIDS at a cross-roads. 2024 Available from: https://www.unaids.org/en/resources/documents/2024/global-aids-update-2024
  2. Singh S. Sahu D. Agrawal A. Vashi M.D. Barriers and opportunities for improving childhood immunization coverage in slums: A qualitative study. Prev. Med. Rep. 2019 14 100858 10.1016/j.pmedr.2019.100858 30997325
    [Google Scholar]
  3. Agócs M. Ismail A. Kamande K. Reasons why children miss vaccinations in Western Kenya; A step in a five-point plan to improve routine immunization. Vaccine 2021 39 34 4895 4902 10.1016/j.vaccine.2021.02.071 33744047
    [Google Scholar]
  4. Goo L. Chohan V. Nduati R. Overbaugh J. Early development of broadly neutralizing antibodies in HIV-1-infected infants. Nat. Med. 2014 20 6 655 658 10.1038/nm.3565 24859529
    [Google Scholar]
  5. Lucier A. Fong Y. Li S.H. Frequent development of broadly neutralizing antibodies in early life in a large cohort of children with human immunodeficiency virus. J. Infect. Dis. 2022 225 10 1731 1740 10.1093/infdis/jiab629 34962990
    [Google Scholar]
  6. McGuire E.P. Fong Y. Toote C. HIV-exposed infants vaccinated with an MF59/Recombinant gp120 vaccine have higher-magnitude Anti-V1V2 IgG responses than adults immunized with the same vaccine. J. Virol. 2017 92 1 92 29021402
    [Google Scholar]
  7. Herati R.S. Wherry E.J. What is the predictive value of animal models for vaccine efficacy in humans? Cold Spring Harb. Perspect. Biol. 2018 10 4 a031583 10.1101/cshperspect.a031583 28348037
    [Google Scholar]
  8. Gerdts V. Wilson H.L. Meurens F. Large animal models for vaccine development and testing. ILAR J. 2015 56 1 53 62 10.1093/ilar/ilv009 25991698
    [Google Scholar]
  9. Stamatatos L. Pancera M. McGuire A.T. Germline‐targeting immunogens. Immunol. Rev. 2017 275 1 203 216 10.1111/imr.12483 28133796
    [Google Scholar]
  10. Sanders R.W. Moore J.P. Progress on priming HIV-1 immunity. Science 2024 384 6697 738 739 10.1126/science.adp3459 38753801
    [Google Scholar]
  11. Rosenberg Y.J. Jiang X. Cheever T. Protection of newborn macaques by plant-derived HIV broadly neutralizing antibodies: A model for passive immunotherapy during breastfeeding. J. Virol. 2021 95 18 e00268 e21 10.1128/JVI.00268‑21 34190597
    [Google Scholar]
  12. Pegu A. Yang Z. Boyington J.C. Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci. Transl. Med. 2014 6 243 243ra88 10.1126/scitranslmed.3008992 24990883
    [Google Scholar]
  13. Mascola J.R. Stiegler G. VanCott T.C. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat. Med. 2000 6 2 207 210 10.1038/72318 10655111
    [Google Scholar]
  14. Baba T.W. Liska V. Hofmann-Lehmann R. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat. Med. 2000 6 2 200 206 10.1038/72309 10655110
    [Google Scholar]
  15. Corey L. Gilbert P.B. Juraska M. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. N. Engl. J. Med. 2021 384 11 1003 1014 10.1056/NEJMoa2031738 33730454
    [Google Scholar]
  16. Gilbert P.B. Huang Y. deCamp A.C. Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition. Nat. Med. 2022 28 9 1924 1932 10.1038/s41591‑022‑01953‑6 35995954
    [Google Scholar]
  17. Liao H.X. Lynch R. Zhou T. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 2013 496 7446 469 476 10.1038/nature12053 23552890
    [Google Scholar]
  18. Doria-Rose N.A. Landais E. Coevolution of HIV-1 and broadly neutralizing antibodies. Curr. Opin. HIV AIDS 2019 14 4 286 293 10.1097/COH.0000000000000550 30994504
    [Google Scholar]
  19. Freund N.T. Wang H. Scharf L. Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller. Sci. Transl. Med. 2017 9 373 eaal2144 10.1126/scitranslmed.aal2144 28100831
    [Google Scholar]
  20. Caniels T.G. Medina-Ramírez M. Zhang J. Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions. Cell Rep. Med. 2023 4 4 101003 10.1016/j.xcrm.2023.101003 37044090
    [Google Scholar]
  21. Bonsignori M. Hwang K.K. Chen X. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J. Virol. 2011 85 19 9998 10009 10.1128/JVI.05045‑11 21795340
    [Google Scholar]
  22. Leggat D.J. Cohen K.W. Willis J.R. Vaccination induces HIV broadly neutralizing antibody precursors in humans. Science 2022 378 6623 eadd6502 10.1126/science.add6502 36454825
    [Google Scholar]
  23. Cohen K.W. De Rosa S.C. Fulp W.J. A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses. Sci. Transl. Med. 2023 15 697 eadf3309 10.1126/scitranslmed.adf3309 37224227
    [Google Scholar]
  24. Medina-Ramírez M. Garces F. Escolano A. Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo. J. Exp. Med. 2017 214 9 2573 2590 10.1084/jem.20161160 28847869
    [Google Scholar]
  25. Sun C. Zuo T. Wen Z. First clinical study of germline-targeting strategy: One step closer to a successful bnAb-based HIV vaccine. Innovation 2023 4 1 100374 10.1016/j.xinn.2023.100374 36747593
    [Google Scholar]
  26. Gristick H.B. Hartweger H. Loewe M. CD4 binding site immunogens elicit heterologous anti-HIV-1 neutralizing antibodies in transgenic and wild-type animals. Sci. Immunol. 2023 8 80 eade6364 10.1126/sciimmunol.ade6364 36763635
    [Google Scholar]
  27. Simonich C.A. Williams K.L. Verkerke H.P. HIV-1 neutralizing antibodies with limited hypermutation from an infant. Cell 2016 166 1 77 87 10.1016/j.cell.2016.05.055 27345369
    [Google Scholar]
  28. Kumar S. Panda H. Makhdoomi M.A. An HIV-1 broadly neutralizing antibody from a clade C-infected pediatric elite neutralizer potently neutralizes the contemporaneous and autologous evolving viruses. J. Virol. 2019 93 4 e01495 e18 10.1128/JVI.01495‑18 30429339
    [Google Scholar]
  29. Sok D. Pauthner M. Briney B. A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans. Immunity 2016 45 1 31 45 10.1016/j.immuni.2016.06.026 27438765
    [Google Scholar]
  30. Steichen J.M. Kulp D.W. Tokatlian T. HIV vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies. Immunity 2016 45 3 483 496 10.1016/j.immuni.2016.08.016 27617678
    [Google Scholar]
  31. Steichen J.M. Phung I. Salcedo E. Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Science 2024 384 6697 eadj8321 10.1126/science.adj8321 38753769
    [Google Scholar]
  32. Verkoczy L. Diaz M. Holl T.M. Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance. Proc. Natl. Acad. Sci. USA 2010 107 1 181 186 10.1073/pnas.0912914107 20018688
    [Google Scholar]
  33. Huang J. Ofek G. Laub L. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 2012 491 7424 406 412 10.1038/nature11544 23151583
    [Google Scholar]
  34. Schiffner T. Phung I. Ray R. Vaccination induces broadly neutralizing antibody precursors to HIV gp41. Nat. Immunol. 2024 25 6 1073 1082 10.1038/s41590‑024‑01833‑w 38816615
    [Google Scholar]
  35. Williams W.B. Alam S.M. Ofek G. Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans. Cell 2024 187 12 2919 2934.e20 10.1016/j.cell.2024.04.033 38761800
    [Google Scholar]
  36. Erdmann N.B. Williams W.B. Walsh S.R. A HIV-1 Gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals. medRxiv 2024 10.1101/2024.03.15.24304305
    [Google Scholar]
  37. Doria-Rose N.A. Schramm C.A. Gorman J. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 2014 509 7498 55 62 10.1038/nature13036 24590074
    [Google Scholar]
  38. Landais E. Murrell B. Briney B. HIV envelope glycoform heterogeneity and localized diversity govern the initiation and maturation of a V2 Apex broadly neutralizing antibody lineage. Immunity 2017 47 5 990 1003.e9 10.1016/j.immuni.2017.11.002 29166592
    [Google Scholar]
  39. Roark R.S. Li H. Williams W.B. Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Science 2021 371 6525 eabd2638 10.1126/science.abd2638 33214287
    [Google Scholar]
  40. Habib R.S. Deep mining of the human antibody repertoire identifies frequent and immunogenetically diverse CDRH3 topologies targetable by vaccination. bioRxiv 2024 10.1101/2024.10.04.616739
    [Google Scholar]
  41. Melzi E. Willis J.R. Ma K.M. Membrane-bound mRNA immunogens lower the threshold to activate HIV Env V2 apex-directed broadly neutralizing B cell precursors in humanized mice. Immunity 2022 55 11 2168 2186.e6 10.1016/j.immuni.2022.09.003 36179690
    [Google Scholar]
  42. Haynes B.F. Wiehe K. Alam S.M. Weissman D. Saunders K.O. Progress with induction of HIV broadly neutralizing antibodies in the duke consortia for HIV/AIDS vaccine development. Curr. Opin. HIV AIDS 2023 18 6 300 308 10.1097/COH.0000000000000820 37751363
    [Google Scholar]
  43. Gao F. Bonsignori M. Liao H.X. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell 2014 158 3 481 491 10.1016/j.cell.2014.06.022 25065977
    [Google Scholar]
  44. Saunders K.O. Wiehe K. Tian M. Targeted selection of HIV-specific antibody mutations by engineering B cell maturation. Science 2019 366 6470 eaay7199 10.1126/science.aay7199 31806786
    [Google Scholar]
  45. LaBranche C.C. Henderson R. Hsu A. Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. PLoS Pathog. 2019 15 9 1008026 10.1371/journal.ppat.1008026 31527908
    [Google Scholar]
  46. Nelson A.N. Shen X. Vekatayogi S. Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques. bioRxiv 2023
    [Google Scholar]
  47. Simonich C.A. Doepker L. Ralph D. Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage. Nat. Commun. 2019 10 1 2190 10.1038/s41467‑019‑09481‑7 31097697
    [Google Scholar]
  48. Mishra N. Sharma S. Dobhal A. Broadly neutralizing plasma antibodies effective against autologous circulating viruses in infants with multivariant HIV-1 infection. Nat. Commun. 2020 11 1 4409 10.1038/s41467‑020‑18225‑x 32879304
    [Google Scholar]
  49. Ditse Z. Muenchhoff M. Adland E. HIV-1 subtype C-infected children with exceptional neutralization breadth exhibit polyclonal responses targeting known epitopes. J. Virol. 2018 92 17 e00878 e18 10.1128/JVI.00878‑18 29950423
    [Google Scholar]
  50. PrabhuDas M Adkins B Gans H Challenges in infant immunity: Implications for responses to infection and vaccines. Nat. Immunol. 2011 12 3 189 194 10.1038/ni0311‑189
    [Google Scholar]
  51. Semmes E.C. Chen J.L. Goswami R. Burt T.D. Permar S.R. Fouda G.G. Understanding early-life adaptive immunity to guide interventions for pediatric health. Front. Immunol. 2021 11 595297 10.3389/fimmu.2020.595297 33552052
    [Google Scholar]
  52. Pieren D.K.J. Boer M.C. de Wit J. The adaptive immune system in early life: The shift makes it count. Front. Immunol. 2022 13 1031924 10.3389/fimmu.2022.1031924 36466865
    [Google Scholar]
  53. Siegrist C.A. Neonatal and early life vaccinology. Vaccine 2001 19 25-26 3331 3346 10.1016/S0264‑410X(01)00028‑7 11348697
    [Google Scholar]
  54. Siegrist C.A. Aspinall R. B-cell responses to vaccination at the extremes of age. Nat. Rev. Immunol. 2009 9 3 185 194 10.1038/nri2508 19240757
    [Google Scholar]
  55. Zimmermann P. Curtis N. Factors that influence the immune response to vaccination. Clin. Microbiol. Rev. 2019 32 2 e00084 e18 10.1128/CMR.00084‑18 30867162
    [Google Scholar]
  56. Borriello F. Pasquarelli N. Law L. Normal B-cell ranges in infants: A systematic review and meta-analysis. J. Allergy Clin. Immunol. 2022 150 5 1216 1224 10.1016/j.jaci.2022.06.006 35728653
    [Google Scholar]
  57. Campbell A.C. Waller C. Wood J. Aynsley-Green A. Yu V. Lymphocyte subpopulations in the blood of newborn infants. Clin. Exp. Immunol. 1974 18 4 469 482 4549627
    [Google Scholar]
  58. Pihlgren M. Friedli M. Tougne C. Rochat A.F. Lambert P.H. Siegrist C.A. Reduced ability of neonatal and early-life bone marrow stromal cells to support plasmablast survival. J. Immunol. 2006 176 1 165 172 10.4049/jimmunol.176.1.165 16365407
    [Google Scholar]
  59. Kibler A. Budeus B. Küppers R. Seifert M. The splenic marginal zone in children is characterized by a subpopulation of CD27-negative, Lowly IGHV-mutated B cells. Front. Immunol. 2022 13 825619 10.3389/fimmu.2022.825619 35154145
    [Google Scholar]
  60. Budeus B. Kibler A. Brauser M. Human cord blood B cells differ from the adult counterpart by conserved Ig repertoires and accelerated response dynamics. J. Immunol. 2021 206 12 2839 2851 10.4049/jimmunol.2100113 34117106
    [Google Scholar]
  61. Gustafson C.E. Higbee D. Yeckes A.R. Limited expression of APRIL and its receptors prior to intestinal IgA plasma cell development during human infancy. Mucosal Immunol. 2014 7 3 467 477 10.1038/mi.2013.64 24045575
    [Google Scholar]
  62. Nielsen SCA Roskin KM Jackson KJL Shaping of infant B cell receptor repertoires by environmental factors and infectious disease. Sci Transl Med 2019 11 481 eaat2004 10.1126/scitranslmed.aat2004 30814336
    [Google Scholar]
  63. Mutsaerts E.A.M.L. van Cranenbroek B. Madhi S.A. Impact of nutritional status on vaccine-induced immunity in children living in South Africa: Investigating the B-cell repertoire and metabolic hormones. Vaccine 2024 42 14 3337 3345 10.1016/j.vaccine.2024.04.034 38637212
    [Google Scholar]
  64. Ferguson A.C. Cheung S.S.C. Modulation of immunoglobulin M and G synthesis by monocytes and T lymphocytes in the newborn infant. J. Pediatr. 1981 98 3 385 391 10.1016/S0022‑3476(81)80700‑7 6970800
    [Google Scholar]
  65. Pabst R. Debertin A.S. Todt-Brenneke M. Herden A. Schmiedl A. The postnatal development of the compartments in human lymph nodes up to 15 years of age. Ann. Anat. 2023 250 152140 10.1016/j.aanat.2023.152140 37499700
    [Google Scholar]
  66. Song W. Craft J. T follicular helper cell heterogeneity. Annu. Rev. Immunol. 2024 42 1 127 152 10.1146/annurev‑immunol‑090222‑102834 38060987
    [Google Scholar]
  67. Choi J. Crotty S. Choi Y.S. Cytokines in follicular helper T cell biology in physiologic and pathologic conditions. Immune Netw. 2024 24 1 8 10.4110/in.2024.24.e8 38455461
    [Google Scholar]
  68. Crotty S. T follicular helper cell biology: A decade of discovery and diseases. Immunity 2019 50 5 1132 1148 10.1016/j.immuni.2019.04.011 31117010
    [Google Scholar]
  69. Singh A. Boggiano C. Yin D.E. Precision adjuvants for pediatric vaccines. Sci. Transl. Med. 2024 16 763 eabq7378 10.1126/scitranslmed.abq7378 39231242
    [Google Scholar]
  70. Thomas S. Pak J. Doss-Gollin S. Human in vitro modeling identifies adjuvant combinations that unlock antigen cross-presentation and promote T-helper 1 development in newborns, adults and elders. J. Mol. Biol. 2024 436 4 168446 10.1016/j.jmb.2024.168446 38242283
    [Google Scholar]
  71. Schüller S.S. Barman S. Mendez-Giraldez R. Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro. Commun. Biol. 2024 7 1 709 10.1038/s42003‑024‑06390‑4 38851856
    [Google Scholar]
  72. Chew K. Lee B. Ozonoff A. A protocol for high-throughput screening for immunomodulatory compounds using human primary cells. STAR Protoc 2023 4 3 102405 10.1016/j.xpro.2023.102405 37453068
    [Google Scholar]
  73. Levy O. Suter E.E. Miller R.L. Wessels M.R. Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells. Blood 2006 108 4 1284 1290 10.1182/blood‑2005‑12‑4821 16638933
    [Google Scholar]
  74. Levy O. Zarember K.A. Roy R.M. Cywes C. Godowski P.J. Wessels M.R. Selective impairment of TLR-mediated innate immunity in human newborns: Neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848. J. Immunol. 2004 173 7 4627 4634 10.4049/jimmunol.173.7.4627 15383597
    [Google Scholar]
  75. Dowling D.J. van Haren S.D. Scheid A. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth. JCI Insight 2017 2 6 91020 10.1172/jci.insight.91020 28352660
    [Google Scholar]
  76. Phillips B. Van Rompay K.K.A. Rodriguez-Nieves J. Adjuvant-dependent enhancement of HIV env-specific antibody responses in infant rhesus macaques. J. Virol. 2018 92 20 e01051 e18 10.1128/JVI.01051‑18 30089691
    [Google Scholar]
  77. Nelson A.N. Shen X. Vekatayogi S. Immunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques. Sci. Immunol. 2024 9 98 eadm7097 10.1126/sciimmunol.adm7097 39213340
    [Google Scholar]
  78. Kasturi S.P. Kozlowski P.A. Nakaya H.I. Adjuvanting a simian immunodeficiency virus vaccine with toll-like receptor ligands encapsulated in nanoparticles induces persistent antibody responses and enhanced protection in TRIM5α restrictive macaques. J. Virol. 2017 91 4 e01844 e16 10.1128/JVI.01844‑16 27928002
    [Google Scholar]
  79. Singleton K.L. Joffe A. Leitner W.W. Review: Current trends, challenges, and success stories in adjuvant research. Front. Immunol. 2023 14 1105655 10.3389/fimmu.2023.1105655 36742311
    [Google Scholar]
  80. Garrido C. Curtis A.D. Dennis M. SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques. Sci. Immunol. 2021 6 60 eabj3684 10.1126/sciimmunol.abj3684 34131024
    [Google Scholar]
  81. Milligan E.C. Olstad K. Williams C.A. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci. Transl. Med. 2023 15 685 eadd6383 10.1126/scitranslmed.add6383 36454813
    [Google Scholar]
  82. Afran L. Garcia Knight M. Nduati E. Urban B.C. Heyderman R.S. Rowland-Jones S.L. HIV-exposed uninfected children: A growing population with a vulnerable immune system? Clin. Exp. Immunol. 2014 176 1 11 22 10.1111/cei.12251 24325737
    [Google Scholar]
  83. Arikawa S. Rollins N. Newell M.L. Becquet R. Mortality risk and associated factors in HIV ‐exposed, uninfected children. Trop. Med. Int. Health 2016 21 6 720 734 10.1111/tmi.12695 27091659
    [Google Scholar]
  84. le Roux S.M. Abrams E.J. Nguyen K. Myer L. Clinical outcomes of HIV ‐exposed, HIV ‐uninfected children in sub‐Saharan Africa. Trop. Med. Int. Health 2016 21 7 829 845 10.1111/tmi.12716 27125333
    [Google Scholar]
  85. Reikie B.A. Naidoo S. Ruck C.E. Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life. Clin. Vaccine Immunol. 2013 20 1 33 38 10.1128/CVI.00557‑12 23114697
    [Google Scholar]
  86. Levin M.J. Lindsey J.C. Kaplan S.S. Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa. AIDS 2017 31 1 49 59 10.1097/QAD.0000000000001258 27662551
    [Google Scholar]
  87. Cotugno N. Pallikkuth S. Sanna M. B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa. EBioMedicine 2023 93 104666 10.1016/j.ebiom.2023.104666 37406590
    [Google Scholar]
  88. Borkowsky W. Wara D. Fenton T. Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators. J. Infect. Dis. 2000 181 3 890 896 10.1086/315298 10720509
    [Google Scholar]
  89. Cunningham C.K. Wara D.W. Kang M. Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women. Clin. Infect. Dis. 2001 32 5 801 807 10.1086/319215 11229849
    [Google Scholar]
  90. McFarland E.J. Borkowsky W. Fenton T. Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine. J. Infect. Dis. 2001 184 10 1331 1335 10.1086/323994 11679925
    [Google Scholar]
  91. Johnson D.C. McFarland E.J. Muresan P. Safety and immunogenicity of an HIV-1 recombinant canarypox vaccine in newborns and infants of HIV-1-infected women. J. Infect. Dis. 2005 192 12 2129 2133 10.1086/498163 16288378
    [Google Scholar]
  92. McFarland E.J. Johnson D.C. Muresan P. HIV-1 vaccine induced immune responses in newborns of HIV-1 infected mothers. AIDS 2006 20 11 1481 1489 10.1097/01.aids.0000237363.33994.45 16847402
    [Google Scholar]
  93. Kintu K. Andrew P. Musoke P. Feasibility and safety of ALVAC-HIV vCP1521 vaccine in HIV-exposed infants in Uganda: Results from the first HIV vaccine trial in infants in Africa. J. Acquir. Immune Defic. Syndr. 2013 63 1 1 8 10.1097/QAI.0b013e31827f1c2d 23221981
    [Google Scholar]
  94. Kaleebu P. Njai H.F. Wang L. Immunogenicity of ALVAC-HIV vCP1521 in infants of HIV-1-infected women in Uganda (HPTN 027): The first pediatric HIV vaccine trial in Africa. J. Acquir. Immune Defic. Syndr. 2014 65 3 268 277 10.1097/01.qai.0000435600.65845.31 24091694
    [Google Scholar]
  95. Afolabi M.O. Ndure J. Drammeh A. A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. PLoS One 2013 8 10 78289 10.1371/journal.pone.0078289 24205185
    [Google Scholar]
  96. Njuguna I.N. Ambler G. Reilly M. PedVacc 002: A phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi. Vaccine 2014 32 44 5801 5808 10.1016/j.vaccine.2014.08.034 25173484
    [Google Scholar]
  97. Violari A. Otwombe K. Hahn W. Safety and implementation of phase I randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns. J. Clin. Invest. 2025 135 11 186927 10.1172/JCI186927 40178906
    [Google Scholar]
  98. Fouda G.G. Cunningham C.K. McFarland E.J. Infant HIV type 1 gp120 vaccination elicits robust and durable anti-V1V2 immunoglobulin G responses and only rare envelope-specific immunoglobulin A responses. J. Infect. Dis. 2015 211 4 508 517 10.1093/infdis/jiu444 25170104
    [Google Scholar]
  99. Rerks-Ngarm S. Pitisuttithum P. Nitayaphan S. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 2009 361 23 2209 2220 10.1056/NEJMoa0908492 19843557
    [Google Scholar]
  100. Itell H.L. McGuire E.P. Muresan P. Development and application of a multiplex assay for the simultaneous measurement of antibody responses elicited by common childhood vaccines. Vaccine 2018 36 37 5600 5608 10.1016/j.vaccine.2018.07.048 30087048
    [Google Scholar]
  101. Nanishi E. Dowling D.J. Levy O. Toward precision adjuvants: Optimizing science and safety. Curr. Opin. Pediatr. 2020 32 1 125 138 10.1097/MOP.0000000000000868 31904601
    [Google Scholar]
  102. Hanke T. McMichael A.J. Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nat. Med. 2000 6 9 951 955 10.1038/79626 10973301
    [Google Scholar]
  103. Parks K.R. MacCamy A.J. Trichka J. Overcoming steric restrictions of VRC01 HIV-1 neutralizing antibodies through immunization. Cell Rep. 2019 29 10 3060 3072.e7 10.1016/j.celrep.2019.10.071 31801073
    [Google Scholar]
  104. Scharf L. West A.P. Sievers S.A. Structural basis for germline antibody recognition of HIV-1 immunogens. eLife 2016 5 13783 10.7554/eLife.13783 26997349
    [Google Scholar]
  105. McGuire A.T. Dreyer A.M. Carbonetti S. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science 2014 346 6215 1380 1383 10.1126/science.1259206 25504724
    [Google Scholar]
  106. McGuire A.T. Gray M.D. Dosenovic P. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat. Commun. 2016 7 1 10618 10.1038/ncomms10618 26907590
    [Google Scholar]
  107. Jardine J. Julien J.P. Menis S. Rational HIV immunogen design to target specific germline B cell receptors. Science 2013 340 6133 711 716 10.1126/science.1234150 23539181
    [Google Scholar]
  108. Jardine J.G. Ota T. Sok D. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science 2015 349 6244 156 161 10.1126/science.aac5894 26089355
    [Google Scholar]
  109. Steichen J.M. Lin Y.C. Havenar-Daughton C. A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses. Science 2019 366 6470 eaax4380 10.1126/science.aax4380 31672916
    [Google Scholar]
  110. Martin T.M. Robinson S.T. Huang Y. Discovery medicine - The HVTN’s iterative approach to developing an HIV-1 broadly neutralizing vaccine. Curr. Opin. HIV AIDS 2023 18 6 290 299 10.1097/COH.0000000000000821 37712873
    [Google Scholar]
  111. Luo S. Jing C. Ye A.Y. Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors. Proc. Natl. Acad. Sci. USA 2023 120 1 2217883120 10.1073/pnas.2217883120 36574685
    [Google Scholar]
  112. Mattison J.A. Vaughan K.L. An overview of nonhuman primates in aging research. Exp. Gerontol. 2017 94 41 45 10.1016/j.exger.2016.12.005 27956088
    [Google Scholar]
  113. Otsyula M.G. Miller C.J. Tarantal A.F. Fetal or neonatal infection with attenuated simian immunodeficiency virus results in protective immunity against oral challenge with pathogenic SIVmac251. Virology 1996 222 1 275 278 10.1006/viro.1996.0420 8806509
    [Google Scholar]
  114. Van Rompay K.K.A. Abel K. Lawson J.R. Attenuated poxvirus-based simian immunodeficiency virus (SIV) vaccines given in infancy partially protect infant and juvenile macaques against repeated oral challenge with virulent SIV. J. Acquir. Immune Defic. Syndr. 2005 38 2 124 134 10.1097/00126334‑200502010‑00002 15671796
    [Google Scholar]
  115. Van Rompay K.K.A. Abel K. Earl P. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: Attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV. Vaccine 2010 28 6 1481 1492 10.1016/j.vaccine.2009.11.061 19995539
    [Google Scholar]
  116. Marthas M.L. Van Rompay K.K.A. Abbott Z. Partial efficacy of a VSV-SIV/MVA-SIV vaccine regimen against oral SIV challenge in infant macaques. Vaccine 2011 29 17 3124 3137 10.1016/j.vaccine.2011.02.051 21377510
    [Google Scholar]
  117. Curtis A.D. Dennis M. Eudailey J. HIV Env-specific IgG antibodies induced by vaccination of neonatal rhesus macaques persist and can be augmented by a late booster immunization in infancy. MSphere 2020 5 2 e00162 e20 10.1128/mSphere.00162‑20 32213623
    [Google Scholar]
  118. Curtis A.D. Jensen K. Van Rompay K.K.A. Amara R.R. Kozlowski P.A. De Paris K. A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector‐based vaccine induces simian immunodeficiency virus‐specific systemic and mucosal immune responses in juvenile rhesus macaques. J. Med. Primatol. 2018 47 5 288 297 10.1111/jmp.12372 30204253
    [Google Scholar]
  119. Curtis A.D. Walter K.A. Nabi R. Oral coadministration of an intramuscular DNA/modified vaccinia ankara vaccine for simian immunodeficiency virus is associated with better control of infection in orally exposed infant macaques. AIDS Res. Hum. Retroviruses 2019 35 3 310 325 10.1089/aid.2018.0180 30303405
    [Google Scholar]
  120. Berendam S.J. Morgan-Asiedu P.K. Mangan R.J. Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques. PLoS One 2021 16 12 0256885 10.1371/journal.pone.0256885 34972105
    [Google Scholar]
  121. Dennis M. Eudailey J. Pollara J. Coadministration of CH31 broadly neutralizing antibody does not affect development of vaccine-induced anti-HIV-1 envelope antibody responses in infant rhesus macaques. J. Virol. 2019 93 5 e01783 e18 10.1128/JVI.01783‑18 30541851
    [Google Scholar]
  122. Nelson A.N. Dennis M. Mangold J.F. Leveraging antigenic seniority for maternal vaccination to prevent mother-to-child transmission of HIV-1. NPJ Vaccines 2022 7 1 87 10.1038/s41541‑022‑00505‑w 35907918
    [Google Scholar]
  123. Rahman M. Adeli M. Schellhorn H.E. Jithesh P.V. Levy O. Editorial: Precision vaccinology for infectious diseases. Front. Immunol. 2024 15 1400443 10.3389/fimmu.2024.1400443 38698861
    [Google Scholar]
  124. Zushin P.J.H. Mukherjee S. Wu J.C. FDA Modernization Act 2.0: Transitioning beyond animal models with human cells, organoids, and AI/ML-based approaches. J. Clin. Invest. 2023 133 21 175824 10.1172/JCI175824 37909337
    [Google Scholar]
  125. Oh D.Y. Dowling D.J. Ahmed S. Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures. Mol. Cell. Proteomics 2016 15 6 1877 1894 10.1074/mcp.M115.055541 26933193
    [Google Scholar]
  126. van Haren S.D. Ganapathi L. Bergelson I. In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant. Cytokine 2016 83 99 109 10.1016/j.cyto.2016.04.001 27081760
    [Google Scholar]
  127. Morrocchi E. van Haren S. Palma P. Levy O. Modeling human immune responses to vaccination in vitro. Trends Immunol. 2024 45 1 32 47 10.1016/j.it.2023.11.002 38135599
    [Google Scholar]
  128. Sanchez-Schmitz G. Stevens C.R. Bettencourt I.A. Microphysiologic human tissue constructs reproduce autologous age-specific BCG and HBV primary immunization in vitro. Front. Immunol. 2018 9 2634 10.3389/fimmu.2018.02634 30524426
    [Google Scholar]
  129. Pettengill M.A. van Haren S.D. Levy O. Soluble mediators regulating immunity in early life. Front. Immunol. 2014 5 457 10.3389/fimmu.2014.00457 25309541
    [Google Scholar]
  130. Doss-Gollin S. Thomas S. Brook B. Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen. NPJ Vaccines 2023 8 1 163 10.1038/s41541‑023‑00759‑y 37884538
    [Google Scholar]
  131. Idoko O.T. Smolen K.K. Wariri O. Corrigendum: Clinical protocol for a longitudinal cohort study employing systems biology to identify markers of vaccine immunogenicity in newborn infants in the Gambia and Papua New Guinea. Front Pediatr. 2020 8 610461 10.3389/fped.2020.610461 33313031
    [Google Scholar]
  132. Dowling D.J. Scott E.A. Scheid A. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses. J. Allergy Clin. Immunol. 2017 140 5 1339 1350 10.1016/j.jaci.2016.12.985 28343701
    [Google Scholar]
  133. Saldanha L. Langel Ü. Vale N. In silico studies to support vaccine development. Pharmaceutics 2023 15 2 654 10.3390/pharmaceutics15020654 36839975
    [Google Scholar]
  134. Olawade D.B. Teke J. Fapohunda O. Leveraging artificial intelligence in vaccine development: A narrative review. J. Microbiol. Methods 2024 224 106998 10.1016/j.mimet.2024.106998 39019262
    [Google Scholar]
  135. Mortazavi B. Molaei A. Fard N.A. Multi-epitope vaccines, from design to expression; an in silico approach. Hum. Immunol. 2024 85 3 110804 10.1016/j.humimm.2024.110804 38658216
    [Google Scholar]
  136. Sanders R.W. Moore J.P. Native‐like Env trimers as a platform for HIV ‐1 vaccine design. Immunol. Rev. 2017 275 1 161 182 10.1111/imr.12481 28133806
    [Google Scholar]
  137. Olin A. Henckel E. Chen Y. Stereotypic immune system development in newborn children. Cell 2018 174 5 1277 1292.e14 10.1016/j.cell.2018.06.045 30142345
    [Google Scholar]
  138. Lee A.H. Shannon C.P. Amenyogbe N. Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. Nat. Commun. 2019 10 1 1092 10.1038/s41467‑019‑08794‑x 30862783
    [Google Scholar]
  139. Rhodes S.J. Guedj J. Fletcher H.A. Using vaccine Immunostimulation/Immunodynamic modelling methods to inform vaccine dose decision-making. NPJ Vaccines 2018 3 1 36 10.1038/s41541‑018‑0075‑3 30245860
    [Google Scholar]
/content/journals/chr/10.2174/011570162X366522250721113420
Loading
/content/journals/chr/10.2174/011570162X366522250721113420
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test