Correlation of Vaccine-Elicited Systemic and Mucosal Nonneutralizing Antibody Activities with Reduced Acute Viremia following Intrarectal Simian Immunodeficiency Virus SIV _mac251 Challenge of Rhesus Macaques

Abstract

Cell-mediated immunity and neutralizing antibodies contribute to control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV

Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding

“…First, studies in HIV-1-infected people (8)(9)(10)(11)(12)(13)(14) and in macaques infected with simian immunodeficiency virus (15,16) consistently show an inverse correlation between Fc-mediated effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC) (8,9) or antibody-dependent cell-mediated viral inhibition (ADCVI), and viral loads or decreased disease progression (17). Second, vaccine-elicited protection both in nonhuman primates (18)(19)(20)(21) and in a subset of human subjects in the Vax-004 trial (22) correlates with Fc-mediated effector function often observed in the absence of detectable neutralizing antibodies (18)(19)(20)(21). Similarly, there was an inverse relationship between acquisition of HIV-1 and ADCC in the RV144 trial for a subset of subjects who had low to moderate IgA anti-gp120 titers (23).…”

HIV Envelope-Specific Antibody and Vaccine Efficacy

“…In support of a protective role for ADCVI, significant correlations between ADCVI activity mediated by vaccine-induced antibodies and decreased acute viremia have been reported in both SIV and SHIV rhesus macaque models (Florese et al, 2009;Hidajat et al, 2009;Xiao et al, 2010). Further, passive infusion of anti-SIV immune serum with strong ADCVI activity to newborn rhesus macaques prevented infection from an oral SIV mac251 challenge .…”

“…The vaccine did not induce antibodies able to neutralize primary SIV mac251 , however, the reduced acute viremia was significantly correlated with anti-envelope binding antibodies that mediated ADCC against SIV mac251 -infected cells (Gomez-Roman et al, 2005). Subsequent studies, one involving a comparison of Ad5hr-SIV recombinant priming via the upper respiratory tract versus the oral route followed by SIV gp120 boosting and SIV mac251 www.intechopen.com challenge, and another involving a comparison of Ad5hr-recombinant priming with and without subsequent envelope protein boosting followed by challenge with the chimeric virus SHIV 89.6P , again showed significant correlations of ADCC activity with reduced acute viremia (Hidajat et al, 2009;Xiao et al, 2010). The latter study also revealed a correlation of ADCC activity with reduced chronic viremia.…”

“…Several vaccine approaches have been evaluated in non-human primates for the ability to elicit viral-specific IgA antibodies at genital/rectal sites. These have included tonsillar immunizations with replication-defective SIV (Vagenas et al, 2009), administration of DNA vaccines intranasally or rectally, followed by boosting with MVA recombinants (Bertley et al, 2004;Wang et al, 2004), intradermal or intramuscular administrations of DNA vaccines together with GM-CSF DNA or CCL27 DNA as adjuvants (Lai et al, 2007;Kraynyak et al, 2010) vaginal delivery of trimeric HIV envelope together with Carbopol gel (Cranage et al, 2011), upper respiratory track immunization with replication-competent Ad-recombinants followed by intramuscular boosting with envelope protein (Florese et al, 2009;Hidajat et al, 2009;Xiao et al, 2010), and intramuscular plus intranasal immunization with a gp41 subunit vaccine delivered on virosomes (Bomsel et al, 2011). These have had varying degrees of success in consistently eliciting mucosal IgA antibodies.…”

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

“…However, recent studies show that vaccination with viral vectors such as Ad vectors can elicit Ab-dependent cell-mediated virus inhibition by non-neutralizing antibodies. 46,53 Therefore, antibodies, including non-neutralizing antibodies, will be helpful for the control of HIV/SIV replication.…”