HIV-1 NEUTRALIZING ANTIBODIES IN THE GENITAL AND RESPIRATORY TRACTS OF MICE INTRANASALLY IMMUNIZED WITH OLIGOMERIC GP160

Because mucosal surfaces are a primary route of HIV-1 infection, we ev aluated the mucosal immunogenicity of a candidate HIV-1 vaccine, oligo meric gp160 (o-gp160), In prior studies, parenteral immunization of ra bbits with o-gp160 elicited broad neutralizing serum Ab responses agai nst both T cell Line-adapted HIV-1 and some primary HIV-1 isolates. In this study, nasal immunization of mice with o-gp160, formulated with liposomes containing monophosphoryl lipid A (MPL), MPL-AF, proteosomes , emulsomes, or proteosomes with emulsomes elicited strong gp160-speci fic Ige and IBA responses in serum as well as vaginal, lung, and intes tinal washes and fecal pellets, The genital, respiratory and intestina l Abs were determined to be locally produced, No mucosal immune respon ses were measurable when the immunogen was given s,c, Abs from sera an d from vaginal and lung washes preferentially recognized native forms of monomeric gp120. suggesting no substantial loss in protein tertiary conformation after vaccine formulation and mucosal administration. In hibition of HIV-1(MN) infection of H9 cells was found in sera from mic e immunized intranasally with o-gp160 formulated with liposomes plus M PL, proteosomes, and proteosomes plus emulsomes. Formulations of o-gp1 60 with MPL-AF, proteosomes, emulsomes, or proteosomes plus emulsomes elicited HIV-1(MN)-neutralizing Ab in lung wash, and formulations with proteosomes, emulsomes, or proteosomes plus emulsomes elicited HIV-1( MN)-neutralizing Ab in vaginal wash. These data demonstrate the feasib ility of inducing both systemic and mucosal HIV-1-neutralizing Ab by i ntranasal immunization with an oligomeric gp160 protein.