Martin Plante

Intranasal Immunization with Gonococcal Outer Membrane Preparations Reduces the Duration of Vaginal Colonization of Mice by Neissevia gonorrhoeae

Nasal immunization was studied to determine if it could elicit an immune response capable of preventing vaginal colonization by Neisseria gonorrhoeae or of reducing its duration in the estradiol-treated mouse model. Nasal administration of gonococcal outer membrane (OM) preparations induced the development of systemic and vaginal immune responses that were directed mainly against a limited number of gonococcal OM proteins. The impact of nasal immunization on vaginal colonization by N. gonorrhoeae was evaluated by use of an experimental model, in which mice were treated with estradiol to prolong the infection. Bacterial clearance was significantly faster for mice immunized intranasally with N. gonorrhoeae OM preparations (4.0+/-2.5 days) than for control mice (8.5+/-4.3 days). The estradiol-treated mouse model may serve as a useful tool for the evaluation of potential gonococcal vaccine candidates.

A nasal Proteosome influenza vaccine containing baculovirus-derived hemagglutinin induces protective mucosal and systemic immunity.

The potential for enhancing the immunogenicity of recombinant (baculovirus-derived) influenza hemagglutinin (rHA) was investigated by comparing the immune responses elicited in mice by an intranasal (i.n.) rHA formulated with Proteosomes, with those induced by intramuscular (i.m.) or i.n. rHA alone. The Proteosome-rHA vaccine induced mucosal responses in the respiratory tract, as well as high serum IgG and hemagglutination inhibition (HAI) titers. In contrast, rHA alone given i.m. induced serum IgG without mucosal responses and was ineffective at inducing either mucosal or systemic responses when given i.n. Only mice immunized with the Proteosome-rHA vaccine were completely protected from both death and acute morbidity following live virus challenge, indicating that the i.n. Proteosome-rHA vaccine induced more complete protective immunity than the same doses of unformulated rHA given i.n. or i.m.

Beta-adrenergic receptors in DMBA-induced rat mammary tumors: Correlation with progesterone receptor and tumor growth

SummaryIn order to gain further knowledge about the potential role of catecholamines in mammary carcinoma, we have used the potent β-adrenergic antagonist cyanopindolol (CYP) as iodinated ligand to characterize β-adrenergic receptors in membranes prepared from mammary tumors induced by dimethylbenz(a)anthraene (DMBA) administration in the rat. The binding of [125I]CYP to membrane preparations of DMBA-induced rat mammary tumors is rapid at room temperature, reaching half maximal specific binding at 30 min of incubation. Scatchard analysis of the data indicates that [125I]CYP binds to a single class of high affinity sites (114 ± 2.1 fmoles/mg protein) at an apparent KD value of 38.0 ± 0.3 pM. The order of potency of a series of agonists to compete for [125I]CYP binding is consistent with interaction with a β2-subtype receptor: zinterol > (−)isoproterenol > (−)epinephrine» (−)norepinephrine. In addition, the potency of a series of specific β1, and β2 synthetic compounds to displace [125I]CYP in mammary tumors is similar to their potency in typical β2-adrenergic tissues. The binding of [125I]CYP to DMBA-induced rat mammary tumors shows a marked stereoselectivity, the (−)isomers of isoproterenol and propranolol being 150 and 80 times more potent, respectively, than their respective enantiomers. The autoradiographic localization of [125I]CYP performed on frozen sections revealed the presence of specific β-adrenergic receptors in all the malignant cells. Spontaneous mammary tumors of aging (18–22 months) female rats have high levels of β-adrenergic receptors. Castration decreased the concentration of [125I]CYP binding sites in DMBA-induced mammary tumors. A close correlation was observed between progressing, static, and regressing tumors after ovariectomy and β-adrenergic receptor concentration. The presence of β-adrenergic receptors in mammary tumors as well as the modulation of their level by ovarian hormones provides a mechanism for catecholaminergic influence in mammary cancer tissue.

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

Abstract Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing.

Experimental investigation of a fiber-slab directional coupler

We report experimental results on the coupling properties of a directional coupler made of a single-mode fiber and a multimode planar waveguide. It is shown that such a device is behaving like a band-reject as well as a band-pass filter depending on the distance between the fiber and the slab. The Y-splitting of the coupled beams in the plane of the slab is also analyzed as a function of the wavelength and compared with the theory.