Induction of mucosal and systemic antibody and T-cell responses following prime-boost immunization with novel adjuvanted human immunodeficiency virus-1-vaccine formulations
Autor: | Brad Lewis, Lauren Hudacik, Maria Grazia Ferrari, Nikolai Petrovsky, Phillip D. Markham, DeVon Thompson, Ranajit Pal, Anthony D. Cristillo, Britany Bowen, Lindsey Galmin |
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Rok vydání: | 2010 |
Předmět: |
Immunoglobulin A
Cellular immunity Sexual transmission T-Lymphocytes medicine.medical_treatment Immunization Secondary HIV Antibodies HIV Envelope Protein gp120 Injections Intramuscular Mice 03 medical and health sciences 0302 clinical medicine Immune system Adjuvants Immunologic Neutralization Tests Immunity Virology Vaccines DNA medicine Animals Immunity Mucosal Administration Intranasal 030304 developmental biology AIDS Vaccines Mice Inbred BALB C 0303 health sciences biology Animal Vaccination 3. Good health Immunoglobulin G Vaccines Subunit Immunology HIV-1 biology.protein Female Nasal administration Adjuvant 030215 immunology |
Zdroj: | The Journal of General Virology |
ISSN: | 1465-2099 0022-1317 |
Popis: | As sexual transmission of human immunodeficiency virus-1 (HIV-1) occurs via the mucosa, an ideal HIV-1 vaccine should induce both mucosal and systemic immunity. We therefore sought to evaluate the induction of mucosal responses using a DNA env prime–gp120 protein boost approach in which sequential nasal and parenteral protein administration was performed with two novel carbohydrate-based adjuvants. These adjuvants, Advax-M and Advax-P, were specifically designed for mucosal and systemic immune enhancement, respectively. Murine intranasal immunization with gp120/Advax-M adjuvant elicited gp120-specific IgA in serum and mucosal secretions that was markedly enhanced by DNA priming. Boosting of DNA-primed mice with gp120/Advax-M and gp120/Advax-P by sequential intranasal and intramuscular immunization, or vice versa, elicited persistent mucosal gp120-specific IgA, systemic IgG and memory T- and B-cell responses. Induction of homologous, but not heterologous, neutralizing activity was noted in the sera of all immunized groups. While confirmation of efficacy is required in challenge studies using non-human primates, these results suggest that the combination of DNA priming with sequential nasal and parenteral protein boosting, with appropriate mucosal and systemic adjuvants, could generate strong mucosal and systemic immunity and may block HIV-1 mucosal transmission and infection. |
Databáze: | OpenAIRE |
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