D Zuijdgeest - Academia.edu (original) (raw)

Papers by D Zuijdgeest

Research paper thumbnail of Overexpression of α-2,6-Sialyltransferase in PER.C6® cells leads to increased susceptibility for human influenza strains Submitted for publication

Annual update of the influenza vaccine relies on analysis of antigenic data generated using cultu... more Annual update of the influenza vaccine relies on analysis of antigenic data generated using cultured clinical influenza isolates. However, the culture of infectious influenza virus from clinical specimens has become increasingly unreliable due to the low avidity for the sialic acid receptor of recent influenza A viruses. MDCK cells overexpressing α-2,6-sialyltransferase have been shown to improve primary isolation and growth of these viruses compared to conventional MDCK cells. To test the generality of the approach we have generated a PER. C6 cell line stably overexpressing ST6Gal1, PER.C6-α2,6ST and compared the susceptibility to infection and ability to support growth of recent human influenza strains with that of the parental cells. The data obtained demonstrate that increased expression of SAα2,6Gal did not produce increased viral titres. However, it did result in an increased recovery rate of influenza A viruses from limiting dilutions of virus inoculum. Furthermore, virus was...

Research paper thumbnail of Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Research paper thumbnail of Suitability of PER.C6® cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics

Research paper thumbnail of Highly Conserved Protective Epitopes on Influenza B Viruses

Science, 2012

Influenza Antibodies, Part B With its ability to reassort in animal hosts like pigs and birds, an... more Influenza Antibodies, Part B With its ability to reassort in animal hosts like pigs and birds, and to cause pandemics, influenza A viruses are often in the spotlight. However, a substantial portion of the annual flu burden is also the result of influenza B virus, which is a single influenza type that is characterized by two antigenically and genetically distinct lineages. Dreyfus et al. (p. 1343 , published online 9 August) identify three monoclonal human antibodies that are able to protect against lethal infection with both lineages of influenza B virus in mice. Two antibodies, which bind to distinct regions of the viral hemagluttinin (HA) molecule, neutralize multiple strains from both lineages of influenza B virus, whereas the third antibody binds to the stem region of HA and is able to neutralize both influenza A and B strains. The structural data from these antibodies bound to HA, together with already known antibodies targeting influenza A, may provide clues for designing a un...

Research paper thumbnail of Novel Replication-Incompetent Vector Derived from Adenovirus Type 11 (Ad11) for Vaccination and Gene Therapy: Low Seroprevalence and Non-Cross-Reactivity with Ad5

Journal of Virology, 2004

A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompet... more A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompetent (ΔE1) adenovirus type 11 (Ad11)-based vectors is described. Ad11 vectors are produced on PER.C6/55K cells yielding high-titer vector batches after purification. Ad11 seroprevalence proves to be significantly lower than that of Ad5, and neutralizing antibody titers against Ad11 are low. Ad11 seroprevalence among human immunodeficiency virus-positive (HIV + ) individuals is as low as that among HIV − individuals, independent of the level of immune suppression. The low level of coinciding seroprevalence between Ad11 and Ad35 in addition to a lack of correlation between high neutralizing antibody titers towards either adenovirus strongly suggest that the limited humoral cross-reactive immunity between these two highly related B viruses appears not to preclude the use of both vectors in the same individual. Ad11 transduces primary cells including smooth muscle cells, synoviocytes, and den...

Research paper thumbnail of Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells

Journal of General Virology, 2006

Adenoviral vectors based on adenovirus type 35 (rAd35) have the advantage of low natural vector i... more Adenoviral vectors based on adenovirus type 35 (rAd35) have the advantage of low natural vector immunity and induce strong, insert-specific T- and B-cell responses, making them prime-candidate vaccine carriers. However, severe vector-genome instability of E1-deleted rAd35 vectors was observed, hampering universal use. The instability of E1-deleted rAd35 vector proved to be caused by low pIX expression induced by removal of the pIX promoter, which was located in the E1B region of B-group viruses. Reinsertion of a minimal pIX promoter resulted in stable vectors able to harbour large DNA inserts (>5 kb). In addition, it is shown that replacement of the E4-Orf6 region of Ad35 by the E4-Orf6 region of Ad5 resulted in successful propagation of an E1-deleted rAd35 vector on existing E1-complementing cell lines, such as PER.C6 cells. The ability to produce these carriers on PER.C6 contributes significantly to the scale of manufacturing of rAd35-based vaccines. Next, a stable rAd35 vaccin...

Research paper thumbnail of High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector

Journal of General Virology, 2007

Replication-incompetent adenovirus type 35 (rAd35) represents a potent vaccine carrier that elici... more Replication-incompetent adenovirus type 35 (rAd35) represents a potent vaccine carrier that elicits strong, antigen-specific T- and B-cell responses in diverse preclinical models. Moreover, Ad35 is rare in human populations, resulting in the absence of neutralizing antibodies against this carrier, in contrast to the commonly used rAd5. Therefore, rAd35 is being investigated as a vaccine carrier for a number of diseases for which an effective vaccine is needed, including malaria, AIDS and tuberculosis. However, it can be perceived that effective immunization will require insertion of multiple antigens into adenoviral vectors. We therefore wanted to create rAd35 vectors carrying double expression cassettes, to expand within one vector the number of insertion sites for foreign DNA encoding antigenic proteins. We show that it is possible to generate rAd35 vectors carrying two cytomegalovirus promoter-driven expression cassettes, provided that the polyadenylation signals in each expressi...

Research paper thumbnail of Replication-Deficient Human Adenovirus Type 35 Vectors for Gene Transfer and Vaccination: Efficient Human Cell Infection and Bypass of Preexisting Adenovirus Immunity

Journal of Virology, 2003

Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementi... more Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the identification of human Ad35 as a virus with low global prevalence and the generation of an Ad35 vector plasmid system for easy insertion of heterologous genes. In addition, we have identified the minimal sequence of the Ad35-E1B region (molecular weight, 55,000 [55K]), pivotal for complementation of fully E1-lacking Ad35 vector on PER.C6 cells. After stable insertion of the 55K sequence into PER.C6 cells a cell line was obtained (PER.C6/55K) that efficiently transcomplements both Ad5 and Ad35 vectors. We further demonstrate that transduction with Ad35 is not hampered by preexisting Ad5 immunity and that Ad35 efficiently infects dendritic cells, smooth ...

Research paper thumbnail of Overexpression of α-2,6-Sialyltransferase in PER.C6® cells leads to increased susceptibility for human influenza strains Submitted for publication

Annual update of the influenza vaccine relies on analysis of antigenic data generated using cultu... more Annual update of the influenza vaccine relies on analysis of antigenic data generated using cultured clinical influenza isolates. However, the culture of infectious influenza virus from clinical specimens has become increasingly unreliable due to the low avidity for the sialic acid receptor of recent influenza A viruses. MDCK cells overexpressing α-2,6-sialyltransferase have been shown to improve primary isolation and growth of these viruses compared to conventional MDCK cells. To test the generality of the approach we have generated a PER. C6 cell line stably overexpressing ST6Gal1, PER.C6-α2,6ST and compared the susceptibility to infection and ability to support growth of recent human influenza strains with that of the parental cells. The data obtained demonstrate that increased expression of SAα2,6Gal did not produce increased viral titres. However, it did result in an increased recovery rate of influenza A viruses from limiting dilutions of virus inoculum. Furthermore, virus was...

Research paper thumbnail of Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

Research paper thumbnail of Suitability of PER.C6® cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics

Research paper thumbnail of Highly Conserved Protective Epitopes on Influenza B Viruses

Science, 2012

Influenza Antibodies, Part B With its ability to reassort in animal hosts like pigs and birds, an... more Influenza Antibodies, Part B With its ability to reassort in animal hosts like pigs and birds, and to cause pandemics, influenza A viruses are often in the spotlight. However, a substantial portion of the annual flu burden is also the result of influenza B virus, which is a single influenza type that is characterized by two antigenically and genetically distinct lineages. Dreyfus et al. (p. 1343 , published online 9 August) identify three monoclonal human antibodies that are able to protect against lethal infection with both lineages of influenza B virus in mice. Two antibodies, which bind to distinct regions of the viral hemagluttinin (HA) molecule, neutralize multiple strains from both lineages of influenza B virus, whereas the third antibody binds to the stem region of HA and is able to neutralize both influenza A and B strains. The structural data from these antibodies bound to HA, together with already known antibodies targeting influenza A, may provide clues for designing a un...

Research paper thumbnail of Novel Replication-Incompetent Vector Derived from Adenovirus Type 11 (Ad11) for Vaccination and Gene Therapy: Low Seroprevalence and Non-Cross-Reactivity with Ad5

Journal of Virology, 2004

A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompet... more A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompetent (ΔE1) adenovirus type 11 (Ad11)-based vectors is described. Ad11 vectors are produced on PER.C6/55K cells yielding high-titer vector batches after purification. Ad11 seroprevalence proves to be significantly lower than that of Ad5, and neutralizing antibody titers against Ad11 are low. Ad11 seroprevalence among human immunodeficiency virus-positive (HIV + ) individuals is as low as that among HIV − individuals, independent of the level of immune suppression. The low level of coinciding seroprevalence between Ad11 and Ad35 in addition to a lack of correlation between high neutralizing antibody titers towards either adenovirus strongly suggest that the limited humoral cross-reactive immunity between these two highly related B viruses appears not to preclude the use of both vectors in the same individual. Ad11 transduces primary cells including smooth muscle cells, synoviocytes, and den...

Research paper thumbnail of Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells

Journal of General Virology, 2006

Adenoviral vectors based on adenovirus type 35 (rAd35) have the advantage of low natural vector i... more Adenoviral vectors based on adenovirus type 35 (rAd35) have the advantage of low natural vector immunity and induce strong, insert-specific T- and B-cell responses, making them prime-candidate vaccine carriers. However, severe vector-genome instability of E1-deleted rAd35 vectors was observed, hampering universal use. The instability of E1-deleted rAd35 vector proved to be caused by low pIX expression induced by removal of the pIX promoter, which was located in the E1B region of B-group viruses. Reinsertion of a minimal pIX promoter resulted in stable vectors able to harbour large DNA inserts (>5 kb). In addition, it is shown that replacement of the E4-Orf6 region of Ad35 by the E4-Orf6 region of Ad5 resulted in successful propagation of an E1-deleted rAd35 vector on existing E1-complementing cell lines, such as PER.C6 cells. The ability to produce these carriers on PER.C6 contributes significantly to the scale of manufacturing of rAd35-based vaccines. Next, a stable rAd35 vaccin...

Research paper thumbnail of High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector

Journal of General Virology, 2007

Replication-incompetent adenovirus type 35 (rAd35) represents a potent vaccine carrier that elici... more Replication-incompetent adenovirus type 35 (rAd35) represents a potent vaccine carrier that elicits strong, antigen-specific T- and B-cell responses in diverse preclinical models. Moreover, Ad35 is rare in human populations, resulting in the absence of neutralizing antibodies against this carrier, in contrast to the commonly used rAd5. Therefore, rAd35 is being investigated as a vaccine carrier for a number of diseases for which an effective vaccine is needed, including malaria, AIDS and tuberculosis. However, it can be perceived that effective immunization will require insertion of multiple antigens into adenoviral vectors. We therefore wanted to create rAd35 vectors carrying double expression cassettes, to expand within one vector the number of insertion sites for foreign DNA encoding antigenic proteins. We show that it is possible to generate rAd35 vectors carrying two cytomegalovirus promoter-driven expression cassettes, provided that the polyadenylation signals in each expressi...

Research paper thumbnail of Replication-Deficient Human Adenovirus Type 35 Vectors for Gene Transfer and Vaccination: Efficient Human Cell Infection and Bypass of Preexisting Adenovirus Immunity

Journal of Virology, 2003

Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementi... more Replication-deficient human adenovirus type 5 (Ad5) can be produced to high titers in complementing cell lines, such as PER.C6, and is widely used as a vaccine and gene therapy vector. However, preexisting immunity against Ad5 hampers consistency of gene transfer, immunological responses, and vector-mediated toxicities. We report the identification of human Ad35 as a virus with low global prevalence and the generation of an Ad35 vector plasmid system for easy insertion of heterologous genes. In addition, we have identified the minimal sequence of the Ad35-E1B region (molecular weight, 55,000 [55K]), pivotal for complementation of fully E1-lacking Ad35 vector on PER.C6 cells. After stable insertion of the 55K sequence into PER.C6 cells a cell line was obtained (PER.C6/55K) that efficiently transcomplements both Ad5 and Ad35 vectors. We further demonstrate that transduction with Ad35 is not hampered by preexisting Ad5 immunity and that Ad35 efficiently infects dendritic cells, smooth ...