scholarly journals Recombinant Adenovirus Serotype 26 (Ad26) and Ad35 Vaccine Vectors Bypass Immunity to Ad5 and Protect Nonhuman Primates against Ebolavirus Challenge

2011 ◽  
Vol 85 (9) ◽  
pp. 4222-4233 ◽  
Author(s):  
T. W. Geisbert ◽  
M. Bailey ◽  
L. Hensley ◽  
C. Asiedu ◽  
J. Geisbert ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Recombinant Adenovirus ◽  
Vaccine Vectors ◽  
Adenovirus Serotype

scholarly journals Immunogenicity of Heterologous Prime-Boost Regimens Involving Recombinant Adenovirus Serotype 11 (Ad11) and Ad35 Vaccine Vectors in the Presence of Anti-Ad5 Immunity

2005 ◽  
Vol 79 (15) ◽  
pp. 9694-9701 ◽  
Author(s):  
Angelique A. C. Lemckert ◽  
Shawn M. Sumida ◽  
Lennart Holterman ◽  
Ronald Vogels ◽  
Diana M. Truitt ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Adenovirus ◽  
Human Populations ◽  
Vaccine Vectors ◽  
Adenovirus Serotype ◽  
Immunodeficiency Virus ◽  
High Prevalence ◽  
Boost Vaccine ◽  
Serotype 5 ◽  
Cellular Immune

ABSTRACT The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.

scholarly journals Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver

2007 ◽  
Vol 81 (9) ◽  
pp. 4866-4871 ◽  
Author(s):  
Daniel Stone ◽  
Ying Liu ◽  
Dmitry Shayakhmetov ◽  
Zong-Yi Li ◽  
Shaoheng Ni ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Target Cell ◽  
Recombinant Adenovirus ◽  
Reticuloendothelial System ◽  
Adenovirus Serotype ◽  
Safety And Efficacy ◽  
Liver Sinusoids ◽  
Serotype 5 ◽  
Platelet Aggregates ◽  
Platelet Depletion

ABSTRACT Intravenous (i.v.) delivery of recombinant adenovirus serotype 5 (Ad5) vectors for gene therapy is hindered by safety and efficacy problems. We have discovered a new pathway involved in unspecific Ad5 sequestration and degradation. After i.v. administration, Ad5 rapidly binds to circulating platelets, which causes their activation/aggregation and subsequent entrapment in liver sinusoids. Virus-platelet aggregates are taken up by Kupffer cells and degraded. Ad sequestration in organs can be reduced by platelet depletion prior to vector injection. Identification of this new sequestration mechanism and construction of vectors that avoid it could improve levels of target cell transduction at lower vector doses.

Aerosol-Mediated Delivery of Recombinant Adenovirus to the Airways of Nonhuman Primates

1995 ◽  
Vol 6 (12) ◽  
pp. 1587-1593 ◽  
Author(s):  
Claude Sené ◽  
Abraham Bout ◽  
Jean-Luc Imler ◽  
Huguette Schultz ◽  
Jean-Marie Willemot ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Recombinant Adenovirus

scholarly journals Impact of Recombinant Adenovirus Serotype 35 Priming versus Boosting of a Plasmodium falciparum Protein: Characterization of T- and B-Cell Responses to Liver-Stage Antigen 1

2008 ◽  
Vol 76 (4) ◽  
pp. 1709-1718 ◽  
Author(s):  
Ariane Rodríguez ◽  
Jaap Goudsmit ◽  
Arjen Companjen ◽  
Ratna Mintardjo ◽  
Gert Gillissen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Recombinant Adenovirus ◽  
Antibody Responses ◽  
T Cell Immunity ◽  
Adenovirus Serotype ◽  
Liver Stage ◽  
Cell Responses ◽  
Cell Immunity ◽  
Ifn Γ

ABSTRACT Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite (CS) protein improved significantly when the protein is primed with recombinant adenovirus serotype 35 coding for CS (rAd35.CS). The current study was designed to answer the question whether such an effect can be extended to liver-stage antigens (LSA) of Plasmodium falciparum such as LSA-1. Studies with mice have demonstrated that the LSA-1 protein induces strong antibody response but a weak T-cell immunity. We first identified T-cell epitopes in LSA-1 by use of intracellular gamma interferon (IFN-γ) staining and confirmed these epitopes by means of enzyme-linked immunospot assay and pentamer staining. We show that a single immunization with rAd35.LSA-1 induced a strong antigen-specific IFN-γ CD8+ T-cell response but no measurable antibody response. In contrast, vaccinations with the adjuvanted recombinant LSA-1 protein induced remarkably low cellular responses but strong antibody responses. Finally, both priming and boosting of the adjuvanted protein by rAd35 resulted in enhanced T-cell responses without impairing the level of antibody responses induced by the protein immunizations alone. Furthermore, the incorporation of rAd35 in the vaccination schedule led to a skewing of LSA-1-specific antibody responses toward a Th1-type immune response. Our results show the ability of rAd35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule without impairing the B-cell response.

scholarly journals Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys

2012 ◽  
Vol 86 (18) ◽  
pp. 9590-9598 ◽  
Author(s):  
Jeffrey E. Teigler ◽  
M. Justin Iampietro ◽  
Dan H. Barouch
Keyword(s):  
Immune Responses ◽  
Rhesus Monkeys ◽  
Interleukin 1 ◽  
Experimental Models ◽  
Gamma Interferon ◽  
Vaccine Vectors ◽  
Adenovirus Serotype ◽  
Cytokine Responses ◽  
Serotype 5

Adenovirus (Ad) vaccine vectors have proven highly immunogenic in multiple experimental models, but the innate immune responses induced by these vectors remain poorly characterized. Here we report innate cytokine responses to 5 different Ad vectors in 26 rhesus monkeys. Vaccination with adenovirus serotype 35 (Ad35), Ad26, and Ad48 induced substantially higher levels of antiviral (gamma interferon [IFN-γ], 10-kDa gamma interferon-induced protein [IP-10]) and proinflammatory (interleukin 1 receptor antagonist [IL-1RA], IL-6) cytokines than vaccination with Ad5 on day 1 following immunization.In vitrostudies with capsid chimeric vectors and receptor-blocking monoclonal antibodies suggested that fiber-receptor interactions, as well as other capsid components, were critical for triggering these innate responses. Moreover, multiple cell populations, including dendritic cells, monocytes/macrophages, and T lymphocytes, contributed to these innate cytokine profiles. These data demonstrate that Ad35, Ad26, and Ad48, which utilize CD46 as their primary cellular receptor, induce significantly greater innate cytokine responses than Ad5, which uses the coxsackievirus and adenovirus receptor (CAR). These differences in innate triggering result in markedly different immunologic milieus for the subsequent generation of adaptive immune responses by these vaccine vectors.

scholarly journals Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

2020 ◽  
Vol 26 (11) ◽  
pp. 1694-1700 ◽  
Author(s):  
Lisa H. Tostanoski ◽  
Frank Wegmann ◽  
Amanda J. Martinot ◽  
Carolin Loos ◽  
Katherine McMahan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Nonhuman Primates ◽  
Severe Pneumonia ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Clinical Disease ◽  
High Dose ◽  
Preclinical Studies ◽  
Vaccine Protection ◽  
Adenovirus Serotype

AbstractCoronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1–4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5–7 and nonhuman primates8–10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11–13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

Distribution of Recombinant Adenovirus in the Cerebrospinal Fluid of Nonhuman Primates

1999 ◽  
Vol 10 (14) ◽  
pp. 2347-2354 ◽  
Author(s):  
M.J. Driesse ◽  
J.M. Kros ◽  
C.J.J. Avezaat ◽  
D. Valerio ◽  
C.J. Vecht ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Nonhuman Primates ◽  
Recombinant Adenovirus
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