DNA immunization confers systemic, but not mucosal, protection against enteroinvasive bacteria

Noll, Annette; Bücheler, Nicole; Bohn, Erwin; Schirmbeck, Reinhold; Reimann, Jörg; Autenrieth, Ingo B.

doi:10.1002/(sici)1521-4141(199903)29:03<986::aid-immu986>3.0.co;2-9

Cited by 28 publications

(22 citation statements)

References 39 publications

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“…Clearly, the addition of the M cell ligand protein 1 enhanced the mucosal IgA responses when compared with naked DNA immunizations in this report and others (10,11). The results from this study not only suggest that NALT M cells are targeted by our protein 1, but also do not exclude the possibility that the nasal epithelium may be transfected.…”

Section: Discussioncontrasting

confidence: 54%

“…In fact, the magnitude of these mucosal IgA responses is similar to those obtained with first-generation Salmonella vaccine vectors (30). Importantly, prolonged mucosal IgA responses were observed, which represent an advantage for this method of DNA delivery when compared with conventional DNA immunization (7,10,11). In addition, the prolonged IgA responses resembled the observed time course described for oral immunization with microencapsulated DNA (18,33,34).…”

Section: Discussionmentioning

confidence: 53%

“…Recent evidence shows that DNA vaccination can confer protective immunity against a number of infectious agents including influenza (4,5), herpes simplex virus (6), HIV (7,8), and Borrelia burgdorferi (9) infections. However, naked DNA immunizations have proven less than optimal for stimulating mucosal immunity (7,10,11) because they are administered peripherally as with conventional vaccines. On the other hand, microencapsulated DNA vaccines were shown to effectively elicit protective mucosal responses in a murine rotavirus challenge model (12).…”

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confidence: 99%

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M cell-targeted DNA vaccination

Wang

Csencsits

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

107

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DNA immunization, although attractive, is poor for inducing mucosal immunity, thus limiting its protective value against most infectious agents. To surmount this shortcoming, we devised a method for mucosal transgene vaccination by using an M cell ligand to direct the DNA vaccine to mucosal inductive tissues and the respiratory epithelium. This ligand, reovirus protein 1, when conjugated to polylysine (PL), can bind the apical surface of M cells from nasal-associated lymphoid tissues. Intranasal immunizations with protein 1-PL-DNA complexes produced antigen-specific serum IgG and prolonged mucosal IgA, as well as enhanced cellmediated immunity, made evident by elevated pulmonary cytotoxic T lymphocyte responses. Therefore, targeted transgene vaccination represents an approach for enabling DNA vaccination of the mucosa.

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Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

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M cell-targeted DNA vaccination

Wang

Csencsits

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

107

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“…Thus, intramuscular and intradermal im- (36). Similarly, subcutaneous immunization in mice with HIV-1 gp160 expressing recombinant vaccinia virus induced cytotoxic T lymphocytes only in the spleen but not in Peyer's patches or intestinal lamina propria (3).…”

Section: Discussionmentioning

confidence: 99%

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Stevceva

Álvarez

Lackner

et al. 2002

J Virol

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As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A‫10ء‬ molecule to assess the capacity of the highly attenuated poxvirus NYVAC/simian immunodeficiency virus (SIV) SIV gpe vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIV mac251 by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NYVAC/SIV gpe and the anamnestic response to SIV mac251 at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIV mac Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigenspecific CD8؉ T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIV mac251 challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8 ؉ T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes.

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“…In fact, intramuscular immunization of BALB/c and C57Bl6 mice with naked plasmid DNA (pRc/Yhsp60) encoding Yersinia enterocolitica 60-kDa heat 309 shock protein (Y-HSP60) conferred protection against dissemination of this infection in the spleen but not at the site of mucosal entry. 9 In regards to B cells, the proposed model, based on numerous studies looking into B-cell migration patterns and adhesion molecule expression suggests that primed lymphoid cells from nasal-associated lymphoid tissue (NALT), from Eustachian tube-associated lymphoid tissue (TALT) and bronchus-associated tissue (BALT) preferentially home into nasal and salivary glands, pharyngeal and middle ear mucosa, bronchial and mammary glands, but can also home into urogenital tract. For example, intranasal immunization with a DNA vaccine constructed with the CMV promoter conjugated to env gp160 and rev genes in liposomes induced high levels of mucosal IgA antibodies in feces and vaginal fluids that were able to neutralize HIV-1.…”

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confidence: 99%

Targeting the mucosa: genetically engineered vaccines and mucosal immune responses

2000

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The discovery that inoculation of DNA leads to strong and long lasting immune responses generated enthusiasm to assess the efficacy of various genetically engineered vaccines against mucosally acquired infections. Various techniques have been used to generate the most suitable DNA vaccines, ranging from immunization with naked DNA to utilizing genetically engineered recombinant viruses and bacteria to deliver the DNA. Different DNA vaccine modalities and mucosal immune responses to them have been discussed. It has been shown that even though intramuscular and intradermal immunization with these vaccines generates strong systemic responses, mucosal responses are not induced. It has been proposed that the site of immunization determines mucosal immune responses and that primed lymphocytes preferentially accumulate at sites where they have been induced thus generating the strongest cellular and antibody responses at the site of vaccination. The impact of the site of induction on mucosal immune responses to vaccines is discussed. It is possible to enhance desired vaccine effects in the mucosa and to modify the undesirable side effects. Cytokines such as IL-2, IL-12, IL-15 and IL-18 have been used to enhance CTL activity while IL-5, IL-6 and the chemokine MIP-1␣ have shown the capacity to increase IgA responses to vaccines. Genes and Immunity (2000) 1, 308-315.

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DNA immunization confers systemic, but not mucosal, protection against enteroinvasive bacteria

Cited by 28 publications

References 39 publications

M cell-targeted DNA vaccination

M cell-targeted DNA vaccination

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Targeting the mucosa: genetically engineered vaccines and mucosal immune responses

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DNA immunization confers systemic, but not mucosal, protection against enteroinvasive bacteria

Cited by 28 publications

References 39 publications

M cell-targeted DNA vaccination

M cell-targeted DNA vaccination

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpeRecombinant Vaccine Result in Gag-Specific CD8+T-Cell Responses in Mucosal Tissues of Macaques

Targeting the mucosa: genetically engineered vaccines and mucosal immune responses

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Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques