Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
Name
Lauffenburger-Ackerman Nature Med final.docx
Size
6.4 MB
Format
Unknown
Checksum (MD5)
1f57e0a74cb89c7634c40fcad4702542
Author(s)
Ackerman, Margaret E.
Pittala, Srivamshi
Broge, Thomas
Linde, Caitlyn
Suscovich, Todd J.
Brown, Eric P.
Bradley, Todd
Natarajan, Harini
Lin, Shu
Sassic, Jessica K.
Alternative Title
Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV
Date Issued
September 2018
Journal
Nature Medicine
Publisher
Nature Publishing Group
Citation
Ackerman, Margaret E., et al. “Route of Immunization Defines Multiple Mechanisms of Vaccine-Mediated Protection against SIV.” Nature Medicine, vol. 24, no. 10, Oct. 2018, pp. 1590–98.
Version
Original manuscript
Abstract
Antibodies are the primary correlate of protection for most licensed vaccines; however, their mechanisms of protection vary, ranging from physical blockade to clearance via the recruitment of innate immunity. Here, we uncover striking functional diversity in vaccine-induced antibodies associated with reduced risk of SIV infection in nonhuman primates. While equivalent levels of protection were observed following intramuscular (IM) and aerosol (AE) immunization, reduced risk of infection was associated IgG-driven antibody-dependent monocyte-mediated phagocytosis in the IM vaccinees, and via vaccine-elicited IgA-driven neutrophil-mediated phagocytosis in AE immunized animals. Thus while 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. These data identify orthogonal functional humoral mechanisms, initiated by distinct vaccination routes, pointing to critical correlates of immunity that may support the rational design of a protective vaccine against HIV.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Ragon Institute of MGH, MIT and Harvard
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41591-018-0161-0
