Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles
| Autor: | Paul A, Goepfert, Marnie L, Elizaga, Kelly, Seaton, Georgia D, Tomaras, David C, Montefiori, Alicia, Sato, John, Hural, Stephen C, DeRosa, Spyros A, Kalams, M Juliana, McElrath, Michael C, Keefer, Lindsey R, Baden, Javier R, Lama, Jorge, Sanchez, Mark J, Mulligan, Susan P, Buchbinder, Scott M, Hammer, Beryl A, Koblin, Michael, Pensiero, Chris, Butler, Bernard, Moss, Harriet L, Robinson, Jennifer, Johnson |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Modified vaccinia Ankara Canarypox Time Factors Adolescent viruses T-Lymphocytes Vaccinia virus Biology HIV Antibodies complex mixtures Virus DNA vaccination Placebos chemistry.chemical_compound Young Adult Major Articles and Brief Reports Immunology and Allergy Humans Vaccines Virus-Like Particle AIDS Vaccines Drug Carriers Vaccines Synthetic env Gene Products Human Immunodeficiency Virus Middle Aged Vaccine efficacy biology.organism_classification Virology Vaccination Infectious Diseases chemistry AIDSVAX Immunology HIV-1 Female Vaccinia |
| Zdroj: | The Journal of infectious diseases. 210(1) |
| ISSN: | 1537-6613 |
| Popis: | A human immunodeficiency virus (HIV) vaccine faces the challenge of eliciting immune responses that can prevent the acquisition of virus and the establishment of latency. Vaccine-induced antibodies (Abs) can block infection by directly neutralizing virus [1] and by binding to virus and virus-infected cells to tag them for destruction by the innate immune response [2, 3]. Elicited cytotoxic (ie, CD8+) T cells can modulate the severity of infection and slow disease progression by recognizing and killing infected cells. The one vaccine to achieve at least partial prevention of infection (efficacy, 31.2%) was tested in Thailand in the RV144 trial [4]. This vaccine regimen consisted of 2 recombinant canarypox primes (ALVAC-HIV vCP1521), followed by 2 canarypox plus bivalent gp120 protein in alum boosts (AIDSVAX B/E) [5]. The elicited Abs had limited ability to neutralize tier 1 HIV isolates, which are easy to neutralize, and no detectable neutralizing activity for tier 2 viruses, which are more difficult to neutralize and characteristic of most currently circulating viruses [6]. In the correlates of risk analysis, the primary immune response that reduced the risk of infection was the binding of Abs to variable loops 1 and 2 of HIV envelope glycoprotein (Env) [7–9]. Provocatively, certain circulating Env-specific immunoglobulin A (IgA) appeared to decrease vaccine efficacy by competing with immunoglobulin G (IgG) binding and Fcγ-initiated mechanisms of protection, such as Ab-dependent cellular cytotoxicity [7, 10, 11]. Nonneutralizing Ab, induced by the RV144 vaccine regimen, captured infectious virions [12]. The binding and neutralizing Ab responses elicited in RV144 rapidly waned, falling by ≥10-fold in the first 6 months [6, 13]. Efficacy also fell with time, from an estimated 60% at peak vaccine response to |
| Databáze: | OpenAIRE |
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