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

Margaret E Ackerman, Jishnu Das, Srivamshi Pittala, Thomas Broge, Caitlyn Linde, Todd J Suscovich, Eric P Brown, Todd Bradley, Harini Natarajan, Shu Lin, et al.
(2018) NATURE MEDICINE. 24(10). p.1590-1598
Author
Organization
Abstract
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.
Keywords
HUMAN-IGG SUBCLASSES, RHESUS-MONKEYS, EFFECTOR FUNCTION, HUMORAL IMMUNITY, HIGH-THROUGHPUT, SHIV CHALLENGE, FC-RECEPTOR, HIV, BINDING, MODELS

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Citation

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MLA
Ackerman, Margaret E., et al. “Route of Immunization Defines Multiple Mechanisms of Vaccine-Mediated Protection against SIV.” NATURE MEDICINE, vol. 24, no. 10, 2018, pp. 1590–98, doi:10.1038/s41591-018-0161-0.
APA
Ackerman, M. E., Das, J., Pittala, S., Broge, T., Linde, C., Suscovich, T. J., … Alter, G. (2018). Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV. NATURE MEDICINE, 24(10), 1590–1598. https://doi.org/10.1038/s41591-018-0161-0
Chicago author-date
Ackerman, Margaret E, Jishnu Das, Srivamshi Pittala, Thomas Broge, Caitlyn Linde, Todd J Suscovich, Eric P Brown, et al. 2018. “Route of Immunization Defines Multiple Mechanisms of Vaccine-Mediated Protection against SIV.” NATURE MEDICINE 24 (10): 1590–98. https://doi.org/10.1038/s41591-018-0161-0.
Chicago author-date (all authors)
Ackerman, Margaret E, Jishnu Das, Srivamshi Pittala, Thomas Broge, Caitlyn Linde, Todd J Suscovich, Eric P Brown, Todd Bradley, Harini Natarajan, Shu Lin, Jessica K Sassic, Sean O’Keefe, Nickita Mehta, Derrick Goodman, Magdalena Sips, Joshua A Weiner, Georgia D Tomaras, Barton F Haynes, Douglas A Lauffenburger, Chris Bailey-Kellogg, Mario Roederer, and Galit Alter. 2018. “Route of Immunization Defines Multiple Mechanisms of Vaccine-Mediated Protection against SIV.” NATURE MEDICINE 24 (10): 1590–1598. doi:10.1038/s41591-018-0161-0.
Vancouver
1.
Ackerman ME, Das J, Pittala S, Broge T, Linde C, Suscovich TJ, et al. Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV. NATURE MEDICINE. 2018;24(10):1590–8.
IEEE
[1]
M. E. Ackerman et al., “Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV,” NATURE MEDICINE, vol. 24, no. 10, pp. 1590–1598, 2018.
@article{8575231,
  abstract     = {{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.}},
  author       = {{Ackerman, Margaret E and Das, Jishnu and Pittala, Srivamshi and Broge, Thomas and Linde, Caitlyn and Suscovich, Todd J and Brown, Eric P and Bradley, Todd and Natarajan, Harini and Lin, Shu and Sassic, Jessica K and O'Keefe, Sean and Mehta, Nickita and Goodman, Derrick and Sips, Magdalena and Weiner, Joshua A and Tomaras, Georgia D and Haynes, Barton F and Lauffenburger, Douglas A and Bailey-Kellogg, Chris and Roederer, Mario and Alter, Galit}},
  issn         = {{1078-8956}},
  journal      = {{NATURE MEDICINE}},
  keywords     = {{HUMAN-IGG SUBCLASSES,RHESUS-MONKEYS,EFFECTOR FUNCTION,HUMORAL IMMUNITY,HIGH-THROUGHPUT,SHIV CHALLENGE,FC-RECEPTOR,HIV,BINDING,MODELS}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1590--1598}},
  title        = {{Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIV}},
  url          = {{http://doi.org/10.1038/s41591-018-0161-0}},
  volume       = {{24}},
  year         = {{2018}},
}
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