International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations

Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Vaccine (Impact Factor: 3.62). 05/2011; 29(32):5203-9. DOI: 10.1016/j.vaccine.2011.05.025
Source: PubMed

ABSTRACT Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×10(10)vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.

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Available from: Surita Roux, Mar 10, 2014
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    • "In the HIV field, Ad5 was used as a booster immunization following DNA priming and induced strong CD8+ T cell responses in a large proportion of the STEP study vaccinees (Buchbinder et al., 2008; McElrath et al., 2008). However, clinical efficacy may have been significantly compromised by pre-existing neutralizing antibodies (ranging from 40 to 70% in developed countries and greater than 90% in developing countries) and cellular immunity (Fitzgerald et al., 2003; Holterman et al., 2004; Bangari and Mittal, 2006; Xiang et al., 2006; Lasaro and Ertl, 2009; Ersching et al., 2010; Mast et al., 2010; Barouch et al., 2011). These results were recapitulated in a non-human primate study using low-dose penile exposure to SIVmac251 in Ad5 seropositive animals immunized with SIV- Gag/Pol/Nef (Qureshi et al., 2012). "
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    ABSTRACT: Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy.
    Frontiers in Microbiology 08/2014; 5:439. DOI:10.3389/fmicb.2014.00439 · 3.99 Impact Factor
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    • "In addition to poxvirus vectors, adenoviral-vectored vaccines have been found to be potent vectors for inducing and boosting T-cell responses to recombinant transgene products.13,14,15 However, the widespread seroprevalence of antibodies to common human adenovirus serotype-5 (AdHu5)16 limits the utility of these viruses as vaccine vectors in humans and was implicated in the failure of an human immunodeficiency virus vaccine to demonstrate efficacy.17 Simian adenoviruses do not suffer from the same limitation, and we have constructed a novel replication-deficient chimpanzee adenovirus vector18 expressing conserved influenza antigens NP and M1 (ChAdOx1 NP+M1). "
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    ABSTRACT: Adenoviruses are potent vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same drawbacks. We have constructed a replication-deficient chimpanzee adenovirus-vectored vaccine expressing the conserved influenza antigens, nucleoprotein and matrix protein 1. Here we report safety and T-cell immunogenicity following vaccination with this novel recombinant simian adenovirus, ChAdOx1 NP+M1, in a first in human dose escalation study using a 3+3 study design, followed by boosting with MVA expressing the same antigens in some volunteers. We demonstrate ChAdOx1 NP+M1 to be safe and immunogenic. ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection.Molecular Therapy (2013); doi:10.1038/mt.2013.284.
    Molecular Therapy 12/2013; 22(3). DOI:10.1038/mt.2013.284 · 6.23 Impact Factor
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    • "Given that these are less likely to be neutralized in humans during vaccination, we and others have tested them as alternatives to Ad5 [24]. In this work, we cloned the genomes from three low seroprevalent species D adenoviruses [21,25,26] and modified these to carry antigens from influenza. We have compared these vaccines to the Ad5 benchmark vaccine by intramuscular and intranasal routes of vaccination to protect mice from a stringent lethal challenge by influenza virus. "
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    ABSTRACT: Seasonal and pandemic influenza remains a constant threat. While standard influenza vaccines have great utility, the need for improved vaccine technologies have been brought to light by the 2009 swine flu pandemic, highly pathogenic avian influenza infections, and the most recent early and widespread influenza activity. Species C adenoviruses based on serotype 5 (AD5) are potent vehicles for gene-based vaccination. While potent, most humans are already immune to this virus. In this study, low seroprevalent species D adenoviruses Ad26, 28, and 48 were cloned and modified to express the influenza virus A/PR/8/34 hemagglutinin gene for vaccine studies. When studied in vivo, these species D Ad vectors performed quite differently as compared to species C Ad vectors depending on the route of immunization. By intramuscular injection, species D vaccines were markedly weaker than species C vaccines. In contrast, the species D vaccines were equally efficient as species C when delivered mucosally by the intranasal route. Intranasal adenovirus vaccine doses as low as 10(8) virus particles per mouse induced complete protection against a stringent lethal challenge dose of influenza. These data support translation of species D adenoviruses as mucosal vaccines and highlight the fundamental effects of differences in virus tropism on vaccine applications.
    PLoS ONE 08/2013; 8(8):e73313. DOI:10.1371/journal.pone.0073313 · 3.23 Impact Factor
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