Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 8: Mucosal Immunity
P08.01
Natural Killer Cells Present in Gut Mucosa as
Potential ADCC Effector Cells
M. Sips 1 , G. Sciaranghella 2 , N. Tong 2 , D. Kwon 2 , P. Brouckaert 1 ,
G. Alter 2
1 Ghent University, Ghent, Belgium; 2 Ragon Institute, USA,
Charlestown, MA, USA
Background: Data from the RV144 HIV vaccine trial showed
a moderate protection from HIV infection in the absence of
neutralizing antibodies or CTL activity. In contrast, all vaccinees
mounted robust HIV-specific binding antibodies, that may have
provided some level of protection through their capacity to
recruit antibody dependent cellular cytotoxicity (ADCC). The
capacity of an antibody to recruit ADCC relies on its ability to
interact with the Fc-receptor, FCγRIII (CD16), expressed on
Natural Killer (NK) cells. However, little is known about innate
immune effector cells present within mucosa, and whether they
have the capacity to be harnessed by ADCC inducing antibodies
should they be elicited by a vaccine. Here we hypothesized
that abundant numbers of CD16+ NK cells line the gut mucosa,
providing a robust effector arm that could be harnessed by ADCC
inducing antibodies.
Methods: The frequency and function of CD16+ cells in the colon
was assessed by flow cytometry following enzymatic digestion of
intestinal resections from HIV-uninfected subjects.
Results: Significantly fewer NK cells were found in colon
resections compared to peripheral blood of healthy controls
(median: 10.40% vs. 18.80%, p=0.0062, respectively).
Furthermore, while both CD56bright immunoregulatory and
CD56dim cytolytic NK cells able to mediate ADCC were present in
the gut, the frequency of these 2 subsets was altered compared
to the blood. Moreover, fewer NK cells expressed NKp46,
NKG2A, KIR, CD8, perforin, and importantly CD16 in the gut
compared to the blood. However, gut NK cells demonstrated
similar to blood cytolytic activity upon stimulation.
Conclusion: Taken together, these data suggest that ADCC inducing
antibodies present within the gut mucosa may likely recruit the
antiviral activities of NK cells. Greater emphasis should be placed
on developing innate immune recruiting antibody assays that
measure the capacity of antibodies to recruit the antiviral activity
of innate immune cells present within mucosal membranes where
transmission occurs.
190
AIDS Vaccine 2012
P08.02
Mucosal Prime with a Replicating Vaccinia-Based
Vaccine Promotes Mucosal Immunity Against SIV
X. Tang 1 , Y. Du 1 , C. Sun 2 , L. Chen 2 , L. Zhang 3 , Z. Chen 1
1 AIDS Institute, LKS Faculty of Medicine, The University of
Hong Kong, Hong Kong, Hong Kong; 2 Institute of Biomedicine
and Health, Chinese Academy of Sciences, Guangzhou, China;
3 Comprehensive AIDS Research Center, Tsinghua University,
Beijing, China
Background: We previously demonstrated that vaccine prime
with a recombinant replication-competent modified vaccinia
Tiantan (rMVTTSIVgpe) was able to enhance the boost effects of a
rAd5SIVgpe for eliciting protective immunity against SIV mucosal
challenge in rhesus macaques. Whether this heterologous prime
and boost regimen is able to elicit potent mucosal immunity
specific to SIV remains less understood.
Methods: Different groups of mice were immunized with the
following regiments: rMVTTSIVgpe-rAd5SIVgpe, rAd5SIVgperMVTTSIVgpe
and rAd5SIVgpe-rAd5SIVgpe. rMVTTSIVgpe was
administrated through intraoral and intranasal routes (ioin)
routes whereas rAd5SIVgpe was given through the intramuscular
injection (im).
Results: Consistent with previous findings in macaques,
mice immunized with the rMVTTSIVgpe-rAd5SIVgpe regimen
generated significantly stronger systemic cellular immune
responses as well as serum antibody responses than any other
vaccine regimens. Furthermore, as compared with other groups,
this rMVTTSIVgpe-rAd5SIVgpe regimen induced significantly
higher frequencies of gut-homing CCR9+ Gag-specific CD8+ T
cells as well as CCR6+ Gag-specific CD4+ and CD8+ T cells. This
regimen also elicited the highest level of CD8+ T cell ELIspot
responses against Gag, Pol and Env antigens in mesenteric
lymph nodes (mLN). Besides, SIV-specific IgGs could be detected
in the rectal wash of mice received rMVTTSIVgpe-rAd5SIVgpe
immunization with detectable neutralizing activity.
Conclusion: These findings demonstrated that mucosal priming
with rMVTTSIVgpe significantly promoted mucosal immunity
against SIV, which may have implications to the effectiveness
of the mucosal rMVTTSIVgpe prime-systemic rAd5SIVgpe
boost vacciniation strategy in preventing mucosal infection of
SIVmac239 in macaques.