Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.

TitleLive simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.
Publication TypeJournal Article
Year of Publication2014
AuthorsLi 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, Waterman D, R Reeves K, Masek-Hammerman K, Derdeyn CA, Alpert MD, Evans DT, Kohler H, Müller S, Robinson J, Lifson JD, Burton DR, R Johnson P, Haase AT
JournalJ Immunol
Volume193
Issue6
Pagination3113-25
Date Published09/15/2014
ISSN1550-6606
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.

DOI10.4049/jimmunol.1400820
Alternate JournalJ. Immunol.
PubMed ID25135832
PubMed Central IDPMC4157131
Grant ListHHSN261200800001E / CA / NCI NIH HHS / United States
HHSN272201100023C / AI / NIAID NIH HHS / United States
P01 AI071306 / AI / NIAID NIH HHS / United States
P51 RR000168 / RR / NCRR NIH HHS / United States
R21 AI086922 / AI / NIAID NIH HHS / United States
R37 AI055332 / AI / NIAID NIH HHS / United States
U19 AI095985 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
1
Cover Picture: