1. Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.
- Author
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Li Q, Zeng M, Duan L, Voss JE, Smith AJ, Pambuccian S, Shang L, Wietgrefe S, Southern PJ, Reilly CS, Skinner PJ, Zupancic ML, Carlis JV, Piatak M Jr, Waterman D, Reeves RK, Masek-Hammerman K, Derdeyn CA, Alpert MD, Evans DT, Kohler H, Müller S, Robinson J, Lifson JD, Burton DR, Johnson RP, and Haase AT
- Subjects
- Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antibody Formation immunology, Cervix Uteri virology, Female, HIV Envelope Protein gp41 immunology, HIV Infections immunology, HIV Infections prevention & control, HIV-1 immunology, Immunoglobulin G biosynthesis, Immunoglobulin G immunology, Macaca mulatta, Mucous Membrane immunology, SAIDS Vaccines administration & dosage, Simian Acquired Immunodeficiency Syndrome immunology, Vaccination, Vaccines, Attenuated administration & dosage, Vaccines, Attenuated immunology, Vagina virology, Cervix Uteri immunology, SAIDS Vaccines immunology, Simian Acquired Immunodeficiency Syndrome prevention & control, Simian Immunodeficiency Virus immunology, Vagina immunology
- Abstract
We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1., (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Published
- 2014
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