Nasal immunization with group B streptococci can induce high levels of specific IgA antibodies in cervicovaginal secretions of mice

Hordnes, Knut; Tynning, Turid; Brown, Thomas A.; Haneberg, Bjørn; Jönsson, Roland

doi:10.1016/s0264-410x(97)00021-2

Cited by 40 publications

(26 citation statements)

References 44 publications

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“…This also suggests the possibility of primed IgA-IgB cells migrating from the upper respiratory tract into the lung, thereby bolstering pulmonary immunity against infections found initially in nasal passages. Thus, our data support the efforts to use intranasal immunization to enhance immunity at other mucosal sites (12)(13)(14)33), as well as throughout the respiratory tract.…”

Section: Discussionsupporting

confidence: 78%

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

et al. 2001

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The purpose of the present study was to determine the extent of immunologic responses, particularly immunopathologic responses, within the upper and lower respiratory tracts after intranasal immunization using the mucosal adjuvant cholera toxin (CT). BALB/c mice were nasally immunized with influenza virus vaccine combined with CT. The inclusion of the mucosal adjuvant CT clearly enhanced generation of antibody responses in both the nasal passages and lungs. After nasal immunization, antigen-specific immunoglobulin A (IgA) antibody-forming cells dominated antibody responses throughout the respiratory tract. However, IgG responses were significant in lungs but not in nasal passages. Furthermore, parenteral immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, whereas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions, characterized by mononuclear cell infiltration, developed within the lungs of mice but not in nasal passages. Lowering dosages of CT reduced, but did not eliminate, these adverse reactions without compromising adjuvancy. Serum IgE responses were also enhanced in a dose-dependent manner by inclusion of CT. In summary, there are differences in the generation of humoral immunity between the upper respiratory tract and the lung. As the upper respiratory tract is in a separate compartment of the immune system from that stimulated by parenteral immunization, nasal immunization is an optimal approach to generate immunity throughout the respiratory tract. Despite the promise of nasal immunization, there is also the potential to develop adverse immunopathologic reactions characterized by pulmonary airway inflammation and IgE production.

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Section: Discussionsupporting

confidence: 78%

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

et al. 2001

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“…route increased only the tracheopulmonary IgG responses, inoculation of CT did not increase the serum or tracheopulmonary antibody responses. The lack of adjuvanticity of CT on antibody responses has been previously reported (1,17). It has been proposed that this reduction might be characteristic of whole-cell vaccines or other particulate antigens, possibly because CT induces tolerance to the immunogen or redirects the immune response toward itself (1).…”

Section: Discussionmentioning

confidence: 87%

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis

et al. 2004

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Cry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatal Naegleria fowleri infection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleri responses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route with N. fowleri lysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 ؋ 10 4 live N. fowleri trophozoites was achieved for immunization by the intranasal route. Intranasal immunization of N. fowleri lysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense against N. fowleri infection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines.

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“…The control mice (gray bars) were not boosted. Anti-FHA IgA (left panels) and IgG (right panels) were measured at three different time points (7,14, and 28 days) after the boost. Results are expressed as mean Ϯ the SEM of four to five mice per group and per time point.…”

Section: Discussionmentioning

confidence: 99%

Genital Antibody Responses in Mice after Intranasal Infection with an Attenuated Candidate Vector Strain of Bordetella pertussis

et al. 2000

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Intranasal administration of live attenuated Bordetella pertussis, from which the pertussis toxin gene has been deleted, has previously been shown to give rise to high levels of serum immunoglobulin G (IgG) antibodies against both the protective antigen filamentous hemagglutinin (FHA) and heterologous antigens genetically fused to FHA. Here, we extend these results by demonstrating that anti-FHA IgA and IgG antibodies are also produced in the genital tract of mice, both in the vagina and in the uterus, after a single intranasal administration of B. pertussis. By comparing the immune responses induced after infection with wild-type virulent B. pertussis with that induced by infection with an attenuated pertussis toxin-deficient strain, we conclude that pertussis toxin produced by the virulent bacteria does not modify antibody production to FHA in the genital tract of B. pertussis-infected mice. The intranasal infection with either the attenuated or the virulent B. pertussis strain also led to the development of immunologic memory that could be efficiently boosted with purified FHA administered either intranasally or intravaginally to give rise to a significant increase in the levels of specific IgA and IgG produced locally in the genital tract, as well as of specific antibodies in the serum. These observations suggest that attenuated B. pertussis could be a promising vector for intranasal administration to induce antibody responses against antigens from sexually transmitted pathogens fused to FHA.Sexually transmitted viral and bacterial infections of the genital tract are common worldwide and cause significant morbidity. To date, no vaccine is available against such infections as caused, for example, by herpes simplex virus (HSV), human immunodeficiency virus, Chlamydia trachomatis, Neisseria gonorrhoeae, group B streptococcus (GBS), and Haemophilus ducreyi. Protective immunity against many of these sexually transmitted pathogens has been associated with local production of specific immunoglobulin G (IgG) and secretory IgA (5,12,20,22,29). In addition, the levels of specific circulating antibodies also appear to be important, since passive transfer of specific maternal IgG to the fetus can block neonatal infection with GBS (9). Moreover, systemic antibodies against HIV and HSV-2, in addition to local immunity, could potentially help to control the dissemination of such genital infection. Based on these notions, a single-dose vaccine that could be administered by a mucosal route and was able to induce local production of specific IgA and IgG antibodies in the genital tract, as well as high levels of specific antibodies in the serum, would appear to be very promising for preventing sexually transmitted diseases. However, the production of specific local antibodies in the genital tract is generally difficult to achieve. Recently, several studies with a replicating live-virus vector (6, 11) have demonstrated the efficiency of intranasal delivery for inducing genital immunity.A live, genetically engineered attenuated ...

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Nasal immunization with group B streptococci can induce high levels of specific IgA antibodies in cervicovaginal secretions of mice

Cited by 40 publications

References 44 publications

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization

Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis

Genital Antibody Responses in Mice after Intranasal Infection with an Attenuated Candidate Vector Strain of Bordetella pertussis

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