Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
| Autor: | Sean O’Keefe, Derrick Goodman, Nickita Mehta, Douglas A. Lauffenburger, Thomas Broge, Eric P. Brown, Jessica K. Sassic, Caitlyn Linde, Srivamshi Pittala, Magdalena Sips, Mario Roederer, Harini Natarajan, Todd J. Suscovich, Shu Lin, Georgia D. Tomaras, Joshua A. Weiner, Todd Bradley, Jishnu Das, Barton F. Haynes, Galit Alter, Margaret E. Ackerman, Chris Bailey-Kellogg |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Primates
0301 basic medicine Canarypox Simian Acquired Immunodeficiency Syndrome Injections Intramuscular Article Antibodies General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Phagocytosis Immunity Administration Inhalation Animals Humans AIDS Vaccines Vaccines Innate immune system biology Drug Administration Routes Vaccine trial General Medicine biology.organism_classification Immunity Innate Immunoglobulin Fc Fragments Vaccination Disease Models Animal 030104 developmental biology Immunization Immunoglobulin G Humoral immunity Immunology biology.protein Simian Immunodeficiency Virus Antibody 030215 immunology |
| Zdroj: | Nature Medicine. 24:1590-1598 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/s41591-018-0161-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink