Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Topic 8: Mucosal Immunity
P08.11
Strong SIV gp120-Specific IgG/IgA Responses in Milk
of African Green Monkeys May Contribute to the
Rarity of Postnatal Transmission in This Species
J.D. Amos 1 , A.B. Wilks 2 , G.G. Fouda 1 , S.D. Smith 3 , G.R. Overman 1 ,
K. Beck 3 , M.A. Moody 1 , G.D. Tomaras 1 , S.R. Permar 1
1 Duke Human Vaccine Institute, Durham, NC, USA; 2 Division
of Viral Pathogenesis, Beth Israel Deaconess Medical Center,
Boston, MA, USA; 3 Division of Laboratory Animal Resources,
Duke University, Durham, NC, USA
Background: African green monkeys (AGMs), natural SIV hosts,
sustain nonpathogenic infections and rarely transmit the virus to
their suckling infants, despite exposure to high milk virus RNA
loads. Furthermore, we previously reported strong autologous
neutralization responses in milk of SIV-infected AGMs which could
contribute to impediment of infant virus acquisition. Comparing
mucosal B cell populations and responses in milk of AGMs to that
of rhesus monkeys (RMs), symptomatic SIV hosts with high rates
of postnatal transmission, could elucidate the protection against
postnatal virus transmission in natural SIV hosts.
Methods: Six female AGMs and four female RMs were hormonallyinduced
into lactation prior to intravenous inoculation with
SIVsab92018 and SIVmac251, respectively. B cells in milk and
blood were phenotypically analyzed by flow cytometry. Total and
SIV gp120-specific IgG/IgA responses in milk and plasma were
measured using autologous virus-specific ELISA.
Results: SIV gp120-specific IgG responses were approximately
one log higher in milk (p=0.02) and plasma (p=0.009) of AGMs
compared to that of RMs. Remarkably, the milk SIV gp120-specific
IgA response of AGMs was two logs higher than that of RMs
(p=0.009). Comparing the milk SIV gp120-specific IgA responses
to other mucosal compartments of AGMs, milk responses were
higher than rectal (p = 0.03), but similar to vaginal responses.
Although there were no significant differences in the milk
memory B cells populations of AGMs and RMs, we observed
a reduced proportion and absolute number of naive B cells
(CD20+, IgD+, CD27-) in milk of RMs (median = 7.9%, 0.16 cells/
µl) compared to AGMs (median = 26.5%, 4.2 cells/µl) (p = 0.009
and 0.06, respectively) during chronic infection.
Conclusion: AGMs appear to preserve SIV-specific IgG/IgA
responses in milk during chronic infection, potentially due to
a lack of immune activation and B cell dysfunction, which may
contribute to the rarity of postnatal SIV transmission in this
natural host species.
P08.12
AIDS Vaccine 2012
Posters
Semen Modulates the Differentiation of Monocyte-
Derived Dendritic Cells Towards a Tolerogenic Profile
F. Remes Lenicov 1 , C. Rodríguez Rodrigues 1 , C. Jancic 1 ,
J. Sabatté 1 , M. Cabrini 1 , M. Donalson 2 , R. Pasqualini Jr 2 ,
J. Geffner 1 , A. Ceballos 1
1 Instituto de Investigaciones Biomedicas en Retrovirus y SIDA,
Buenos Aires, Argentina; 2 Instituto Médico Halitus, Buenos
Aires, Argentina
Background: HIV vaccines have not been able to provide immune
protection against sexually-transmitted HIV. We hypothesized
that semen has an active role in the transmission of HIV by
influencing the early events of the immune response. This study
analyzed the ability of spermatozoa and seminal plasma (SP) to
modulate in vitro the differentiation profile of human monocytederived
dendritic cells (DC).
Methods: Spermatozoa were purified by swim-up of semen
samples from healthy donors, while SP was obtained by semen
centrifugation. DC were obtained by incubating peripheral blood
monocytes (>85% purity) with GM-CSF and IL-4 for 5 days, in
the absence or presence of spermatozoa (Sp: monocyte ratio
4:1) or SP (dilution 1:5000). DC phenotype was analyzed by flow
cytometry while cytokine production was measured by ELISA.
Results: Differentiation of DC performed in the presence of
spermatozoa or SP resulted in a marked reduction of CD1a
expreession together with increased expression of CD14. The
mean fluorescence intensity for CD1a was: 7464 ± 106, 210 ± 25
and 766 ± 35 (p