Non-neutralizing IgG anti-PID antibodies decreased viral load following high dose vaginal challenge of non-human primates.

MOOG, C; DEREUDDRE-BOSQUET, NATHALIE; BIEDMA, M.E.; SCHMIDT, S; DECOVILLE, T; HOLL, V; VCELAR, BRITTA; KATTINGER, DITMAR; MANGEOT, ISABELLE; LE GRAND, ROGER

Boston

Congreso; AIDS Vaccine; 2012

Background: Fc-mediated inhibitory activity of neutralizingantibodies has been shown to participate in HIV protection(Hessell et al. 2007). In addition, a non-neutralizing antibodyF240 was found to partially protect macaques from SHIV vaginaltransmission (Moore et al., 2011). However, mechanismsinvolved in this protection need further investigations. In thisstudy, two non-neutralizing antibodies have been selected onthe basis of their Fc-mediated inhibitory functions in vitro forfurther analysis of their protective role on vaginal challenge innon-human primate (NHP).Methods: We have assessed and scored various in vitroHIV-inhibitory activities of non-neutralizing antibodies: Fcmediatedinhibition of macrophages through phagocytosisof immunecomplexes, ADCC in primary infected CD4+ Tlymphocytes by autologous NK cells, capture of native primaryvirus particles. Efficacy of two anti-PID antibodies with high invitro functional scores has been tested in NHP. The combinationof two antibodies formulated in 1.6% HEC gel has been topicallyapplied in the vagina of macaques (n=6), 1 hour before vaginalchallenge with high dose (10 AID50) of SHIVSF162P3.Infectionwas followed by assessing viral load in the plasma.Results: Although unable to block virus entry at mucosal site asall treated animals became persistently infected, the antibodytreated macaques have significant decrease of plasma viral load(day 7, p=0.0479; day 14, p=0.0351, day 42: p=0.0370).Conclusion: Decrease in viral load following antibody treatmentstrongly suggests that non-neutralizing inhibitory antibodiescould interfere with early viral replication and disseminationthrough Fc-mediated inhibitory functions. Additional studies willbe required to optimize this inhibition, and combined strategiesshould be developed to assess the potential synergy betweenneutralizing and non-neutralizing inhibitory antibodies.