scholarly journals INFECTIOUS VIRUS-ANTIBODY COMPLEX IN THE BLOOD OF CHRONICALLY INFECTED MICE

1966 ◽  
Vol 124 (1) ◽  
pp. 81-97 ◽  
Author(s):  
Abner Louis Notkins ◽  
Suellen Mahar ◽  
Christina Scheele ◽  
Joel Goffman
Keyword(s):  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Lactic Dehydrogenase ◽  
Resistant Virus ◽  
Virus Antibody ◽  
In Vitro Exposure ◽  
Antiviral Antibody ◽  
Antibody Complex

If viremic sera from mice chronically infected with lactic dehydrogenase virus (LDV) were first treated with ether or ultraviolet light to inactivate the infectious virus, neutralizing antibody could be demonstrated. Significant amounts of antibody, however, were not detected until the mice had been infected for about 2½ months and its presence did not result in the elimination of the chronic viremia. Virus isolated from sera containing neutralizing antibody was found to be relatively resistant to neutralization by anti-LDV. Further studies revealed that the resistant virus existed in the form of an infectious virus-antibody complex (sensitized virus). The presence of such a complex was demonstrated by the fact that the virus fraction which persisted after in vivo or in vitro exposure to mouse anti-LDV was readily neutralized by goat anti-mouse sera or goat anti-mouse γ-globulin, whereas virus that had not been previously exposed to mouse anti-LDV was completely resistant to neutralization by goat anti-mouse sera. These findings suggest that (a) sensitization may play an important role in the resistance and susceptibility of a virus to neutralization by antiviral antibody, and (b) an anti-γ-globulin may prove useful in neutralizing the resistant fraction and in demonstrating otherwise undetectable antiviral antibody.

INFECTIOUS VIRUS-ANTIBODY COMPLEXES: INTERACTION WITH ANTI-IMMUNOGLOBULINS, COMPLEMENT, AND RHEUMATOID FACTOR

1971 ◽  
Vol 134 (3) ◽  
pp. 41-51 ◽  
Author(s):  
Abner Louis Notkins
Keyword(s):  
Rheumatoid Factor ◽  
Immune Complex ◽  
Complex Disease ◽  
Infectious Virus ◽  
Immune Complex Disease ◽  
Virus Antibody ◽  
Extensive Coverage ◽  
Antiviral Antibody

Interaction of antiviral antibody with the virion can result in the formation of infectious VA complexes. These complexes have been recovered from the blood of chronically infected animals and have been produced in vitro. Incubation of infectious VA complexes with specific anti-immunoglobulins or the purified first and fourth components of complement resulted in neutralization. With subneutralizing concentrations of the first and fourth components of complement, neutralization was enhanced by the addition of the second and third components of complement. RF attached to infectious VA complexes but failed to produce neutralization. The attachment of RF to VA complexes, however, increased the susceptibility of these complexes to neutralization by complement. These findings support the hypothesis that anti-immunoglobulins and complement result in neutralization by more extensive coverage of the surface of the virion than occurs with antiviral antibody alone. Other experiments showed that antiviral antibody increased the sedimentation of radio-labeled virus and that rate-zonal centrifugation could be used to purify VA complexes and to study factors which influence the association and dissociation of these complexes. Our experiments suggest that in vivo the attachment of accessory factors to infectious VA complexes might enhance virus neutralization and play a role in the pathogenesis of virus-induced immune complex disease.

scholarly journals Effect of Preexisting Immunity on an Adenovirus Vaccine Vector: In Vitro Neutralization Assays Fail To Predict Inhibition by Antiviral Antibody In Vivo

2009 ◽  
Vol 83 (11) ◽  
pp. 5567-5573 ◽  
Author(s):  
Susan L. Pichla-Gollon ◽  
Shih-Wen Lin ◽  
Scott E. Hensley ◽  
Marcio O. Lasaro ◽  
Larissa Herkenhoff-Haut ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Human Adenovirus ◽  
T Cell Response ◽  
Fundamental Properties ◽  
High Prevalence ◽  
Antiviral Antibody ◽  
Adenovirus Vectors

ABSTRACT A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8+ T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8+ T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.

scholarly journals Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Naïve Mice and Those with Preexisting Immunity

2011 ◽  
Vol 19 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Jin Huk Choi ◽  
Joe Dekker ◽  
Stephen C. Schafer ◽  
Jobby John ◽  
Craig E. Whitfill ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Transduction Efficiency ◽  
Virus Antibody ◽  
Cell Responses

ABSTRACTThe immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity.In vitroandin vivoassays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P= 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.

scholarly journals In vitro exposure to cadmium in rat L6 myoblasts can result in both enhancement and suppression of malignant progression in vivo

1996 ◽  
Vol 17 (6) ◽  
pp. 1349-1356 ◽  
Author(s):  
Michael K. Abshire ◽  
Deborah E. Devor ◽  
Bhalchandra A. Diwan ◽  
John D. Shaughnessy ◽  
Michael P. Waalkes
Keyword(s):  
Malignant Progression ◽  
In Vitro Exposure

scholarly journals Single cell RNA sequencing of calvarial and long bone endocortical cells

2019 ◽  
Author(s):  
Ugur M. Ayturk ◽  
Joseph P. Scollan ◽  
Alexander Vesprey ◽  
Christina M. Jacobsen ◽  
Paola Divieti Pajevic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cultured Cells ◽  
Neutralizing Antibody ◽  
Long Bone ◽  
Appendicular Skeleton ◽  
Rna Seq ◽  
Isolated Cells

ABSTRACTSingle cell RNA-seq (scRNA-seq) is emerging as a powerful technology to examine transcriptomes of individual cells. We determined whether scRNA-seq could be used to detect the effect of environmental and pharmacologic perturbations on osteoblasts. We began with a commonly used in vitro system in which freshly isolated neonatal mouse calvarial cells are expanded and induced to produce a mineralized matrix. We used scRNA-seq to compare the relative cell type abundances and the transcriptomes of freshly isolated cells to those that had been cultured for 12 days in vitro. We observed that the percentage of macrophage-like cells increased from 6% in freshly isolated calvarial cells to 34% in cultured cells. We also found that Bglap transcripts were abundant in freshly isolated osteoblasts but nearly undetectable in the cultured calvarial cells. Thus, scRNA-seq revealed significant differences between heterogeneity of cells in vivo and in vitro. We next performed scRNA-seq on freshly recovered long bone endocortical cells from mice that received either vehicle or Sclerostin-neutralizing antibody for 1 week. Bone anabolism-associated transcripts were also not significantly increased in immature and mature osteoblasts recovered from Sclerostin-neutralizing antibody treated mice; this is likely a consequence of being underpowered to detect modest changes in gene expression, since only 7% of the sequenced endocortical cells were osteoblasts, and a limited portion of their transcriptomes were sampled. We conclude that scRNA-seq can detect changes in cell abundance, identity, and gene expression in skeletally derived cells. In order to detect modest changes in osteoblast gene expression at the single cell level in the appendicular skeleton, larger numbers of osteoblasts from endocortical bone are required.

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