Intermediate Levels of Pre-Existing Protective Antibody Allow Priming of Protective T Cell Immunity against Influenza.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

Influenza, Human* ; Influenza A Virus, H1N1 Subtype* ; Influenza Vaccines* ; Influenza A virus* ; Orthomyxoviridae Infections*; Animals ; Mice ; Humans ; Influenza A Virus, H3N2 Subtype ; CD8-Positive T-Lymphocytes ; Antibodies, Viral ; Immune Sera

Overcoming interfering impacts of pre-existing immunity to generate universally protective influenza A virus (IAV)-specific T cell immunity through vaccination is a high priority. In this study, we passively transfer varied amounts of H1N1-IAV-specific immune serum before H1N1-IAV infection to determine how different levels of pre-existing Ab influence the generation and protective potential of heterosubtypic T cell responses in a murine model. Surprisingly, IAV nucleoprotein-specific CD4 and CD8 T cell responses are readily detected in infected recipients of IAV-specific immune serum regardless of the amount transferred. When compared with responses in control groups and recipients of low and intermediate levels of convalescent serum, nucleoprotein-specific T cell responses in recipients of high levels of IAV-specific serum, which prevent overt weight loss and reduce peak viral titers in the lungs, are, however, markedly reduced. Although detectable at priming, this response recalls poorly and is unable to mediate protection against a lethal heterotypic (H3N2) virus challenge at later memory time points. A similar failure to generate protective heterosubtypic T cell immunity during IAV priming is seen in offspring of IAV-primed mothers that naturally receive high titers of IAV-specific Ab through maternal transfer. Our findings support that priming of protective heterosubtypic T cell responses can occur in the presence of intermediate levels of pre-existing Ab. These results have high relevance to vaccine approaches aiming to incorporate and evaluate cellular and humoral immunity towards IAV and other viral pathogens against which T cells can protect against variants escaping Ab-mediated protection.
(Copyright © 2023 by The American Association of Immunologists, Inc.)

Cell. 2021 Feb 18;184(4):861-880. (PMID: 33497610)
J Immunol. 2001 Jun 15;166(12):7437-45. (PMID: 11390496)
J Immunol. 1985 Mar;134(3):1994-8. (PMID: 3155776)
Lancet. 1979 Jan 6;1(8106):33-5. (PMID: 83475)
Science. 2021 Dec 03;374(6572):abm0829. (PMID: 34648302)
J Virol. 2011 Nov;85(22):11995-2000. (PMID: 21880755)
J Immunol. 2007 Jan 15;178(2):1030-8. (PMID: 17202366)
J Infect Dis. 2011 Sep 15;204(6):845-53. (PMID: 21846636)
Lancet Infect Dis. 2016 Aug;16(8):942-51. (PMID: 27061888)
Vaccine. 2021 Mar 12;39(11):1598-1608. (PMID: 33612341)
Lancet Infect Dis. 2009 Dec;9(12):784-8. (PMID: 19879807)
Sci Transl Med. 2013 Aug 28;5(200):200ra114. (PMID: 23986398)
Emerg Infect Dis. 2006 Jan;12(1):48-54. (PMID: 16494717)
Nat Med. 2010 May;16(5):558-64, 1p following 564. (PMID: 20436484)
Nat Med. 2012 Jan 29;18(2):274-80. (PMID: 22286307)
Nat Rev Microbiol. 2021 Jul;19(7):409-424. (PMID: 34075212)
Nat Rev Immunol. 2021 Jun;21(6):382-393. (PMID: 33875867)
mBio. 2017 Mar 21;8(2):. (PMID: 28325769)
Vaccine. 2020 Jan 3;38(1):20-28. (PMID: 31672332)
J Immunol. 2004 May 1;172(9):5553-60. (PMID: 15100298)
Mol Cell. 2017 Feb 2;65(3):403-415.e8. (PMID: 28132841)
Nat Commun. 2021 Dec 15;12(1):7288. (PMID: 34911947)
Cold Spring Harb Perspect Med. 2021 Nov 1;11(11):. (PMID: 32988981)
J Infect Dis. 2023 Feb 1;227(3):381-390. (PMID: 35199825)
Lancet. 2012 Dec 15;380(9859):2095-128. (PMID: 23245604)
Cell. 2020 Nov 12;183(4):996-1012.e19. (PMID: 33010815)
Nat Med. 2019 Apr;25(4):591-596. (PMID: 30886409)
Nat Rev Immunol. 2012 Jan 20;12(2):136-48. (PMID: 22266691)
Lancet. 2018 Mar 31;391(10127):1285-1300. (PMID: 29248255)
Curr Opin Immunol. 2018 Aug;53:187-195. (PMID: 29890370)
Am J Reprod Immunol. 2022 Jul;88(1):e13550. (PMID: 35452552)
Nat Commun. 2014 Nov 05;5:5377. (PMID: 25369785)
J Infect. 2016 Jul 5;72 Suppl:S83-90. (PMID: 27233120)
J Immunol. 2008 Feb 15;180(4):2562-72. (PMID: 18250467)
Cell Rep. 2022 Feb 15;38(7):110388. (PMID: 35172138)
J Immunol. 2014 Jan 1;192(1):200-5. (PMID: 24273000)
J Immunol. 1994 Feb 15;152(4):1653-61. (PMID: 8120375)
Cell. 2022 Apr 28;185(9):1588-1601.e14. (PMID: 35413241)
EClinicalMedicine. 2019 Jul 26;13:21-30. (PMID: 31517260)
Immunity. 2021 Sep 14;54(9):2133-2142.e3. (PMID: 34453880)
J Exp Med. 1978 Apr 1;147(4):1236-52. (PMID: 306410)
Science. 2014 Nov 21;346(6212):996-1000. (PMID: 25414313)
J Virol. 1987 May;61(5):1375-83. (PMID: 2952806)
Clin Vaccine Immunol. 2011 Sep;18(9):1519-23. (PMID: 21813667)
Clin Infect Dis. 2018 Oct 30;67(suppl_1):S57-S65. (PMID: 30376095)
J Clin Invest. 1997 Nov 1;100(9):2371-5. (PMID: 9410917)
Cell. 2022 Mar 3;185(5):847-859.e11. (PMID: 35139340)
Emerg Themes Epidemiol. 2021 Oct 21;18(1):15. (PMID: 34674730)
Nat Med. 2013 Oct;19(10):1305-12. (PMID: 24056771)
Nat Med. 2006 Oct;12(10):1203-7. (PMID: 16964257)
J Virol. 2011 Dec;85(24):13310-21. (PMID: 21976658)
Vaccine. 2008 Apr 16;26(17):2062-72. (PMID: 18378366)
Immunity. 2010 Jan 29;32(1):79-90. (PMID: 20096607)
PLoS One. 2009;4(5):e5538. (PMID: 19440239)
J Biomed Sci. 2014 Nov 18;21:99. (PMID: 25407417)
Science. 2010 Aug 27;329(5995):1060-4. (PMID: 20647428)
Front Immunol. 2014 Sep 16;5:446. (PMID: 25278941)
Best Pract Res Clin Obstet Gynaecol. 2021 Oct;76:66-82. (PMID: 33129673)
Vaccine. 2021 Jul 30;39(33):4628-4640. (PMID: 34226103)
Br Med Bull. 1979 Jan;35(1):69-75. (PMID: 367490)
Front Immunol. 2015 Feb 24;6:79. (PMID: 25759693)
J Hyg (Lond). 1972 Dec;70(4):767-77. (PMID: 4509641)
J Exp Med. 1998 May 4;187(9):1383-93. (PMID: 9565631)
Sci Immunol. 2021 May 25;6(59):. (PMID: 34035118)
J Immunol. 1991 Mar 15;146(6):1972-8. (PMID: 2005388)
Am J Respir Cell Mol Biol. 2011 May;44(5):692-9. (PMID: 20616357)
J Clin Invest. 2012 Aug;122(8):2847-56. (PMID: 22820287)
Infect Immun. 1984 Jan;43(1):202-5. (PMID: 6606624)
Nat Rev Immunol. 2020 Oct;20(10):633-643. (PMID: 32782358)
Vaccine. 2012 Dec 7;30(51):7407-10. (PMID: 22643217)
Virol J. 2017 Jun 26;14(1):123. (PMID: 28651593)
J Immunol. 2008 Jan 1;180(1):454-63. (PMID: 18097047)
Proc Natl Acad Sci U S A. 2019 Jul 23;116(30):15194-15199. (PMID: 31296560)
PLoS Pathog. 2020 Nov 19;16(11):e1009010. (PMID: 33211756)
J Immunol. 2001 Apr 1;166(7):4627-33. (PMID: 11254721)
Cell Rep. 2022 Apr 12;39(2):110632. (PMID: 35417685)
Sci Transl Med. 2015 Dec 2;7(316):316ra192. (PMID: 26631631)
Science. 2012 Dec 21;338(6114):1634-7. (PMID: 23180776)
Nat Commun. 2020 Sep 11;11(1):4566. (PMID: 32917903)
J Gen Virol. 2010 Jul;91(Pt 7):1743-53. (PMID: 20335492)
PLoS Pathog. 2022 Mar 10;18(3):e1010395. (PMID: 35271686)
J Virol. 2015 Mar;89(6):3308-17. (PMID: 25589639)
J Lab Clin Med. 1988 Nov;112(5):634-40. (PMID: 3183495)
J Infect Dis. 2006 Jan 1;193(1):49-53. (PMID: 16323131)
Curr Protoc Immunol. 2001 May;Chapter 19:Unit 19.11. (PMID: 18432752)
Immunol Rev. 2013 Sep;255(1):149-64. (PMID: 23947353)
Curr Protoc Microbiol. 2009 May;Chapter 15:Unit 15G.3. (PMID: 19412911)
J Virol. 2000 Apr;74(8):3486-93. (PMID: 10729122)
J Immunol. 2013 Aug 1;191(3):1001-5. (PMID: 23794632)
JCI Insight. 2017 Dec 21;2(24):. (PMID: 29263304)
Vaccines (Basel). 2020 Nov 16;8(4):. (PMID: 33207559)
J Exp Med. 2014 Aug 25;211(9):1707-14. (PMID: 25135297)
J Exp Med. 1977 Mar 1;145(3):557-68. (PMID: 233901)
Cold Spring Harb Perspect Biol. 2021 Nov 1;13(11):. (PMID: 33903157)
J Exp Med. 2013 Jul 29;210(8):1493-500. (PMID: 23857983)
J Virol. 2011 Mar;85(6):2695-702. (PMID: 21228239)
J Immunol. 2006 Oct 15;177(8):5317-27. (PMID: 17015717)
PLoS Pathog. 2019 Aug 14;15(8):e1007989. (PMID: 31412088)
Nat Commun. 2018 Dec 21;9(1):5427. (PMID: 30575715)
Clin Immunol. 2006 Apr;119(1):87-94. (PMID: 16386960)
Nature. 2021 Jul;595(7868):572-577. (PMID: 34044428)
PLoS One. 2012;7(3):e33428. (PMID: 22432020)
Cell Rep. 2017 Apr 4;19(1):114-124. (PMID: 28380351)

R01 AI165406 United States AI NIAID NIH HHS; R21 HD093948 United States HD NICHD NIH HHS

0 (Influenza Vaccines)
0 (Antibodies, Viral)
0 (Immune Sera)

Date Created: 20230116 Date Completed: 20230309 Latest Revision: 20240302

20240302

PMC9998374

10.4049/jimmunol.2200393

36645384