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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of an HIV/AIDS vaccine faces formidable challenges related to the high genetic variability of the virus which has developed potent escape mechanisms to dodge the immune responses of the host, while maintaining the immune system in a permanent state of activation that rapidly leads to T cell exhaustion. Our total lack of knowledge on potential immune correlates of protection, our inability to elicit potent broadly neutralizing anti-HIV antibodies by active immunization added to the limitations with the existing animal models are other obstacles to overcome. The field met with its first failure 5 years ago when a gp120-based subunit vaccine showed no protection against HIV infection in two Phase III trials in the USA and Thailand. It recently met with its second failure when the Merck "STEP" trial had to be prematurely interrupted. The trial was a Phase IIb study of an Adenovirus 5 (Ad5)-HIV vaccine meant to elicit a cellular immune response, essentially HIV-specific CD8+ CTLs, to control viremia in the vaccinees who happened to become infected. Not only did the vaccine fail to control the viral loads in the HIV-infected vaccinees, but unexpectedly the number of HIV infections observed in adenovirus-pre-immune volunteers was significantly higher in the vaccine group than in the placebo group. This does not imply that T cell vaccines have no future but illustrates the limitations and risks of that approach. It also suggests that current assays that measure T cell responses are inadequate to assess CTL functionality. Taking into account the failure of these first two generations of HIV/AIDS vaccines, the development of a third generation vaccine is being considered, aiming at setting up a dual humoral and cellular immune barrier to HIV at the mucosal site of entry of the virus.
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PMID:[HIV/AIDS vaccines: heading for new vaccine approaches?]. 1868 Dec 15

Adenovirus-based vectors are powerful vehicles for gene transfer applications in vaccination and gene therapy. Although highly exploited in the clinical setting, key aspects of the adenovirus biology are still not well understood, in particular the subversion of host cell metabolism during viral infection and replication. The aim of this work was to gain insights on the metabolism of two human cell lines (HEK293 and an amniocyte-derived cell line, 1G3) after infection with an adenovirus serotype 5 vector (AdV5). In order to profile metabolic alterations, we used (1)H-NMR spectroscopy, which allowed the quantification of 35 metabolites in cell culture supernatants with low sample preparation and in a relatively short time. Significant differences between both cell lines in non-infected cultures were identified, namely in glutamine and acetate metabolism, as well as by-product secretion. The main response to AdV5 infection was an increase in glucose consumption and lactate production rates. Moreover, cultures performed with or without glutamine supplementation confirmed the exhaustion of this amino acid as one of the main causes of lower AdV5 production at high cell densities (10- and 1.5-fold less specific yields in HEK293 and 1G3 cells, respectively), and highlighted different degrees of glutamine dependency of adenovirus replication in each cell line. The observed metabolic alterations associated with AdV5 infection and specificity of the host cell line can be useful for targeted bioprocess optimization.
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PMID:Impact of Adenovirus infection in host cell metabolism evaluated by (1)H-NMR spectroscopy. 2721 42

Adenovirus (Ad) vectors are being investigated as vaccine candidates, but baseline antivector immunity exists in human populations to both human Ad (HuAd) and chimpanzee Ad (ChAd) vectors. In this study, we investigated the immunogenicity and cross-reactivity of a panel of recently described rhesus adenoviral (RhAd) vectors. RhAd vectors elicited T cells with low exhaustion markers and robust anamnestic potential. Moreover, RhAd vector immunogenicity was unaffected by high levels of preexisting anti-HuAd immunity. Both HuAd/RhAd and RhAd/RhAd prime-boost vaccine regimens were highly immunogenic, despite a degree of cross-reactive neutralizing antibodies (NAbs) between phylogenetically related RhAd vectors. We observed extensive vector-specific cross-reactive CD4 T cell responses and more limited CD8 T cell responses between RhAd and HuAd vectors, but the impact of vector-specific cellular responses was far less than that of vector-specific NAbs. These data suggest the potential utility of RhAd vectors and define novel heterologous prime-boost strategies for vaccine development.IMPORTANCE To date, most adenoviral vectors developed for vaccination have been HuAds from species B, C, D, and E, and human populations display moderate to high levels of preexisting immunity. There is a clinical need for new adenoviral vectors that are not hindered by preexisting immunity. Moreover, the development of RhAd vector vaccines expands our ability to vaccinate against multiple pathogens in a population that may have received other HuAd or ChAd vectors. We evaluated the immunogenicity and cross-reactivity of RhAd vectors, which belong to the poorly described adenovirus species G. These vectors induced robust cellular and humoral immune responses and were not hampered by preexisting anti-HuAd vector immunity. Such properties make RhAd vectors attractive as potential vaccine vectors.
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PMID:Immunogenicity and Cross-Reactivity of Rhesus Adenoviral Vectors. 2956 85