title: Newcastle disease virus expressing human immunodeficiency virus type 1 envelope glycoprotein induces strong mucosal and serum antibody responses in Guinea pigs.
abstract: Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly through mucosal sites. Optimum strategies to elicit both systemic and mucosal immunity are critical for the development of vaccines against HIV-1. We therefore sought to evaluate the induction of systemic and mucosal immune responses by the use of Newcastle disease virus (NDV) as a vaccine vector. We generated a recombinant NDV, designated rLaSota/gp160, expressing the gp160 envelope (Env) protein of HIV-1 from an added gene. The gp160 protein expressed by rLaSota/gp160 virus was detected on an infected cell surface and was incorporated into the NDV virion. Biochemical studies showed that gp160 present in infected cells and in the virion formed a higher-order oligomer that retained recognition by conformationally sensitive monoclonal antibodies. Expression of gp160 did not increase the virulence of recombinant NDV (rNDV) strain LaSota. Guinea pigs were administered rLaSota/gp160 via the intranasal (i.n.) or intramuscular (i.m.) route in different prime-boost combinations. Systemic and mucosal antibody responses specific to the HIV-1 envelope protein were assessed in serum and vaginal washes, respectively. Two or three immunizations via the i.n. or i.m. route induced a more potent systemic and mucosal immune response than a single immunization by either route. Priming by the i.n. route was more immunogenic than by the i.m. route, and the same was true for the boosts. Furthermore, immunization with rLaSota/gp160 by any route or combination of routes induced a Th1-type response, as reflected by the induction of stronger antigen-specific IgG2a than IgG1 antibody responses. Additionally, i.n. immunization elicited a stronger neutralizing serum antibody response to laboratory-adapted HIV-1 strain MN.3. These data illustrate that it is feasible to use NDV as a vaccine vector to elicit potent humoral and mucosal responses to the HIV-1 envelope protein.
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Khattar
authors.forename: Sweety
authors.initials: S
authors.lastname: Samal
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Devico
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary / Q000379:methods; D009522:Newcastle disease virus / Q000235:genetics*; D014611:Vaccination / Q000379:methods
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; C514797:gp160 protein, Human immunodeficiency virus 1