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Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV

Antibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies that is dr... Full description

Journal Title: Nature medicine 2018-10, Vol.24 (10), p.1590-1598
Main Author: Ackerman, Margaret E
Other Authors: Das, Jishnu , Pittala, Srivamshi , Broge, Thomas , Linde, Caitlyn , Suscovich, Todd J , Brown, Eric P , Bradley, Todd , Natarajan, Harini , Lin, Shu , Sassic, Jessica K , O'Keefe, Sean , Mehta, Nickita , Goodman, Derrick , Sips, Magdalena , Weiner, Joshua A , Tomaras, Georgia D , Haynes, Barton F , Lauffenburger, Douglas A , Bailey-Kellogg, Chris , Roederer, Mario , Alter, Galit
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
HIV
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/30177821
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6482471
title: Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
format: Article
creator:
  • Ackerman, Margaret E
  • Das, Jishnu
  • Pittala, Srivamshi
  • Broge, Thomas
  • Linde, Caitlyn
  • Suscovich, Todd J
  • Brown, Eric P
  • Bradley, Todd
  • Natarajan, Harini
  • Lin, Shu
  • Sassic, Jessica K
  • O'Keefe, Sean
  • Mehta, Nickita
  • Goodman, Derrick
  • Sips, Magdalena
  • Weiner, Joshua A
  • Tomaras, Georgia D
  • Haynes, Barton F
  • Lauffenburger, Douglas A
  • Bailey-Kellogg, Chris
  • Roederer, Mario
  • Alter, Galit
subjects:
  • Administration, Inhalation
  • AIDS Vaccines - immunology
  • AIDS Vaccines - therapeutic use
  • Animals
  • Antibodies
  • Antibodies - immunology
  • Article
  • Correlation
  • Deoxyribonucleic acid
  • Disease Models, Animal
  • DNA
  • Dosage and administration
  • Drug Administration Routes
  • Effector cells
  • Health aspects
  • Health risks
  • HIV
  • Human immunodeficiency virus
  • Humans
  • Immunity
  • Immunity, Innate - genetics
  • Immunization
  • Immunoglobulin A
  • Immunoglobulin Fc Fragments - genetics
  • Immunoglobulin Fc Fragments - immunology
  • Immunoglobulin G
  • Immunoglobulin G - immunology
  • Infections
  • Injections, Intramuscular
  • Innate immunity
  • Isotypes
  • Methods
  • Monocytes
  • Phagocytes
  • Phagocytosis
  • Phagocytosis - immunology
  • Prevention
  • Primates
  • Primates - immunology
  • Primates - virology
  • Proteins
  • Risk reduction
  • Simian Acquired Immunodeficiency Syndrome - immunology
  • Simian Acquired Immunodeficiency Syndrome - prevention & control
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus - drug effects
  • Simian Immunodeficiency Virus - immunology
  • Simian Immunodeficiency Virus - pathogenicity
  • Vaccination
  • Vaccines
  • Vaccines - administration & dosage
  • Vaccines - adverse effects
  • Viral antibodies
  • Virus diseases
ispartof: Nature medicine, 2018-10, Vol.24 (10), p.1590-1598
description: Antibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies that is driven by immunization site and is associated with reduced risk of SIV infection in nonhuman primates. While equivalent levels of protection were observed following intramuscular (IM) and aerosol (AE) immunization with an otherwise identical DNA prime-Ad5 boost regimen, reduced risk of infection was associated with IgG-driven antibody-dependent monocyte-mediated phagocytosis in the IM vaccinees, but with vaccine-elicited IgA-driven neutrophil-mediated phagocytosis in AE-immunized animals. Thus, although route-independent correlates indicate a critical role for phagocytic Fc-effector activity in protection from SIV, the site of immunization may drive this Fc activity via distinct innate effector cells and antibody isotypes. Moreover, the same correlates predicted protection from SHIV infection in a second nonhuman primate vaccine trial using a disparate IM canarypox prime-protein boost strategy, analogous to that used in the first moderately protective human HIV vaccine trial. These data identify orthogonal functional humoral mechanisms, initiated by distinct vaccination routes and immunization strategies, pointing to multiple, potentially complementary correlates of immunity that may support the rational design of a protective vaccine against HIV.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleRoute of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
creatorAckerman, Margaret E ; Das, Jishnu ; Pittala, Srivamshi ; Broge, Thomas ; Linde, Caitlyn ; Suscovich, Todd J ; Brown, Eric P ; Bradley, Todd ; Natarajan, Harini ; Lin, Shu ; Sassic, Jessica K ; O'Keefe, Sean ; Mehta, Nickita ; Goodman, Derrick ; Sips, Magdalena ; Weiner, Joshua A ; Tomaras, Georgia D ; Haynes, Barton F ; Lauffenburger, Douglas A ; Bailey-Kellogg, Chris ; Roederer, Mario ; Alter, Galit
creatorcontribAckerman, Margaret E ; Das, Jishnu ; Pittala, Srivamshi ; Broge, Thomas ; Linde, Caitlyn ; Suscovich, Todd J ; Brown, Eric P ; Bradley, Todd ; Natarajan, Harini ; Lin, Shu ; Sassic, Jessica K ; O'Keefe, Sean ; Mehta, Nickita ; Goodman, Derrick ; Sips, Magdalena ; Weiner, Joshua A ; Tomaras, Georgia D ; Haynes, Barton F ; Lauffenburger, Douglas A ; Bailey-Kellogg, Chris ; Roederer, Mario ; Alter, Galit
descriptionAntibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies that is driven by immunization site and is associated with reduced risk of SIV infection in nonhuman primates. While equivalent levels of protection were observed following intramuscular (IM) and aerosol (AE) immunization with an otherwise identical DNA prime-Ad5 boost regimen, reduced risk of infection was associated with IgG-driven antibody-dependent monocyte-mediated phagocytosis in the IM vaccinees, but with vaccine-elicited IgA-driven neutrophil-mediated phagocytosis in AE-immunized animals. Thus, although route-independent correlates indicate a critical role for phagocytic Fc-effector activity in protection from SIV, the site of immunization may drive this Fc activity via distinct innate effector cells and antibody isotypes. Moreover, the same correlates predicted protection from SHIV infection in a second nonhuman primate vaccine trial using a disparate IM canarypox prime-protein boost strategy, analogous to that used in the first moderately protective human HIV vaccine trial. These data identify orthogonal functional humoral mechanisms, initiated by distinct vaccination routes and immunization strategies, pointing to multiple, potentially complementary correlates of immunity that may support the rational design of a protective vaccine against HIV.
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languageeng
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subjectAdministration, Inhalation ; AIDS Vaccines - immunology ; AIDS Vaccines - therapeutic use ; Animals ; Antibodies ; Antibodies - immunology ; Article ; Correlation ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Dosage and administration ; Drug Administration Routes ; Effector cells ; Health aspects ; Health risks ; HIV ; Human immunodeficiency virus ; Humans ; Immunity ; Immunity, Innate - genetics ; Immunization ; Immunoglobulin A ; Immunoglobulin Fc Fragments - genetics ; Immunoglobulin Fc Fragments - immunology ; Immunoglobulin G ; Immunoglobulin G - immunology ; Infections ; Injections, Intramuscular ; Innate immunity ; Isotypes ; Methods ; Monocytes ; Phagocytes ; Phagocytosis ; Phagocytosis - immunology ; Prevention ; Primates ; Primates - immunology ; Primates - virology ; Proteins ; Risk reduction ; Simian Acquired Immunodeficiency Syndrome - immunology ; Simian Acquired Immunodeficiency Syndrome - prevention & control ; Simian immunodeficiency virus ; Simian Immunodeficiency Virus - drug effects ; Simian Immunodeficiency Virus - immunology ; Simian Immunodeficiency Virus - pathogenicity ; Vaccination ; Vaccines ; Vaccines - administration & dosage ; Vaccines - adverse effects ; Viral antibodies ; Virus diseases
ispartofNature medicine, 2018-10, Vol.24 (10), p.1590-1598
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1Das, Jishnu
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3Broge, Thomas
4Linde, Caitlyn
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6Brown, Eric P
7Bradley, Todd
8Natarajan, Harini
9Lin, Shu
10Sassic, Jessica K
11O'Keefe, Sean
12Mehta, Nickita
13Goodman, Derrick
14Sips, Magdalena
15Weiner, Joshua A
16Tomaras, Georgia D
17Haynes, Barton F
18Lauffenburger, Douglas A
19Bailey-Kellogg, Chris
20Roederer, Mario
21Alter, Galit
title
0Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
1Nature medicine
addtitleNat Med
descriptionAntibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies that is driven by immunization site and is associated with reduced risk of SIV infection in nonhuman primates. While equivalent levels of protection were observed following intramuscular (IM) and aerosol (AE) immunization with an otherwise identical DNA prime-Ad5 boost regimen, reduced risk of infection was associated with IgG-driven antibody-dependent monocyte-mediated phagocytosis in the IM vaccinees, but with vaccine-elicited IgA-driven neutrophil-mediated phagocytosis in AE-immunized animals. Thus, although route-independent correlates indicate a critical role for phagocytic Fc-effector activity in protection from SIV, the site of immunization may drive this Fc activity via distinct innate effector cells and antibody isotypes. Moreover, the same correlates predicted protection from SHIV infection in a second nonhuman primate vaccine trial using a disparate IM canarypox prime-protein boost strategy, analogous to that used in the first moderately protective human HIV vaccine trial. These data identify orthogonal functional humoral mechanisms, initiated by distinct vaccination routes and immunization strategies, pointing to multiple, potentially complementary correlates of immunity that may support the rational design of a protective vaccine against HIV.
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1AIDS Vaccines - immunology
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3Animals
4Antibodies
5Antibodies - immunology
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7Correlation
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9Disease Models, Animal
10DNA
11Dosage and administration
12Drug Administration Routes
13Effector cells
14Health aspects
15Health risks
16HIV
17Human immunodeficiency virus
18Humans
19Immunity
20Immunity, Innate - genetics
21Immunization
22Immunoglobulin A
23Immunoglobulin Fc Fragments - genetics
24Immunoglobulin Fc Fragments - immunology
25Immunoglobulin G
26Immunoglobulin G - immunology
27Infections
28Injections, Intramuscular
29Innate immunity
30Isotypes
31Methods
32Monocytes
33Phagocytes
34Phagocytosis
35Phagocytosis - immunology
36Prevention
37Primates
38Primates - immunology
39Primates - virology
40Proteins
41Risk reduction
42Simian Acquired Immunodeficiency Syndrome - immunology
43Simian Acquired Immunodeficiency Syndrome - prevention & control
44Simian immunodeficiency virus
45Simian Immunodeficiency Virus - drug effects
46Simian Immunodeficiency Virus - immunology
47Simian Immunodeficiency Virus - pathogenicity
48Vaccination
49Vaccines
50Vaccines - administration & dosage
51Vaccines - adverse effects
52Viral antibodies
53Virus diseases
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13Goodman, Derrick
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15Weiner, Joshua A
16Tomaras, Georgia D
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titleRoute of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
authorAckerman, Margaret E ; Das, Jishnu ; Pittala, Srivamshi ; Broge, Thomas ; Linde, Caitlyn ; Suscovich, Todd J ; Brown, Eric P ; Bradley, Todd ; Natarajan, Harini ; Lin, Shu ; Sassic, Jessica K ; O'Keefe, Sean ; Mehta, Nickita ; Goodman, Derrick ; Sips, Magdalena ; Weiner, Joshua A ; Tomaras, Georgia D ; Haynes, Barton F ; Lauffenburger, Douglas A ; Bailey-Kellogg, Chris ; Roederer, Mario ; Alter, Galit
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1AIDS Vaccines - immunology
2AIDS Vaccines - therapeutic use
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8Deoxyribonucleic acid
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10DNA
11Dosage and administration
12Drug Administration Routes
13Effector cells
14Health aspects
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23Immunoglobulin Fc Fragments - genetics
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42Simian Acquired Immunodeficiency Syndrome - immunology
43Simian Acquired Immunodeficiency Syndrome - prevention & control
44Simian immunodeficiency virus
45Simian Immunodeficiency Virus - drug effects
46Simian Immunodeficiency Virus - immunology
47Simian Immunodeficiency Virus - pathogenicity
48Vaccination
49Vaccines
50Vaccines - administration & dosage
51Vaccines - adverse effects
52Viral antibodies
53Virus diseases
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8Natarajan, Harini
9Lin, Shu
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0M.E.A., M.R. and G.A. conceived of and designed the study. M.E.A., G.D.T., B.F.H., D.A.L., C.B.-K., M.R. and G.A. supervised experimental and statistical analysis. J.D. and S.P. performed data analysis. T.Broge, C.L., E.P.B., T.Bradley, H.N., S.L., J.K.S., S.O., N.M., D.G., and M.S. performed assays. T.J.S. and J.A.W. aggregated data. M.E.A., J.D., S.P. and G.A. wrote the manuscript.
1contributed equally
2Author contributions
abstractAntibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection may vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies that is driven by immunization site and is associated with reduced risk of SIV infection in nonhuman primates. While equivalent levels of protection were observed following intramuscular (IM) and aerosol (AE) immunization with an otherwise identical DNA prime-Ad5 boost regimen, reduced risk of infection was associated with IgG-driven antibody-dependent monocyte-mediated phagocytosis in the IM vaccinees, but with vaccine-elicited IgA-driven neutrophil-mediated phagocytosis in AE-immunized animals. Thus, although route-independent correlates indicate a critical role for phagocytic Fc-effector activity in protection from SIV, the site of immunization may drive this Fc activity via distinct innate effector cells and antibody isotypes. Moreover, the same correlates predicted protection from SHIV infection in a second nonhuman primate vaccine trial using a disparate IM canarypox prime-protein boost strategy, analogous to that used in the first moderately protective human HIV vaccine trial. These data identify orthogonal functional humoral mechanisms, initiated by distinct vaccination routes and immunization strategies, pointing to multiple, potentially complementary correlates of immunity that may support the rational design of a protective vaccine against HIV.
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