An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge

Rider, Paul J. F.; Kamil, Mohd; Yilmaz, Ilknur; Atmaca, Habibe N; Kalkan-Yazıcı, Merve; Doymaz, Mehmet Ziya; Kousoulas, Konstantin G.; Aly, A. S.

doi:10.3390/vaccines10020300

Cited by 4 publications

(2 citation statements)

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“…Deleting the gK and UL20 binding sites with gB modifies viral entry preventing the virus from entering via the fusion of the viral envelope with cellular membranes, including neuronal axons [ 10 ]. This led to the development of VC2 as a vaccine and oncolytic strain [ 9 , 11 , 14 , 15 , 40 , 41 ]. Herein, we show that inactivation of the UL37 deamidase catalytic site restores the VC2 virus replication and spread defects indicating that this amino acid change alters the ability of the UL37/gK/UL20 complex to function in virus replication and spread.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, VC2 intramuscular immunization of mice and guinea pigs generates protective immune responses against both virulent HSV-1 and HSV-2 infections of genital tissues [ 11 , 12 , 13 , 14 ]. Additionally, VC2 has been utilized as a vector to express malaria and influenza genes to protect against lethal challenges with those pathogens [ 15 , 16 ]. These results suggest that VC2 induces an adjuvant effect.…”

Section: Introductionmentioning

confidence: 99%

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Inactivation of the UL37 Deamidase Enhances Virus Replication and Spread of the HSV-1(VC2) Oncolytic Vaccine Strain and Secretion of GM-CSF

Clark

Jambunathan

Collantes

et al. 2023

Viruses

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The HSV-1 (VC2) live-attenuated vaccine strain was engineered with specific deletions in the amino termini of glycoprotein K (gK) and membrane protein UL20, rendering the virus unable to enter neurons and establish latency. VC2 replicates efficiently in epithelial cell culture but produces lower viral titers and smaller viral plaques than its parental HSV-1 (F) wild-type virus. VC2 is an effective live-attenuated vaccine against HSV-1 and HSV-2 infections in mice and guinea pigs and an anti-tumor immunotherapeutic and oncolytic virus against melanoma and breast cancer in mouse models. Previously, we reported that the gK/UL20 complex interacts with the UL37 tegument protein, and this interaction is essential for virion intracellular envelopment and egress. To investigate the potential role of the UL37 deamidase functions, the recombinant virus FC819S and VC2C819S were constructed with a C819S substitution to inactivate the UL37 predicted deamidase active site on an HSV-1(F) and HSV-1(VC2) genetic background, respectively. FC819S replicated to similar levels with HSV-1(F) and produced similar size viral plaques. In contrast, VC2C819S replication was enhanced, and viral plaques increased in size, approaching those of the wild-type HSV-1(F) virus. FC819S infection of cell cultures caused enhanced GM-CSF secretion in comparison to HSV-1(F) across several cell lines, including HEp2 cells and cancer cell lines, DU145 (prostate) and Panc 04.03 (pancreas), and primary mouse peritoneal cells. VC2 infection of these cell lines caused GM-CSF secretion at similar levels to FC819S infection. However, the VC2C819S virus did not exhibit any further enhancement of GM-CSF secretion compared to the VC2 virus. These results suggest that the UL37 deamidation functions in conjunction with the gK/UL20 complex to facilitate virus replication and GM-CSF secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inactivation of the UL37 Deamidase Enhances Virus Replication and Spread of the HSV-1(VC2) Oncolytic Vaccine Strain and Secretion of GM-CSF

Clark

Jambunathan

Collantes

et al. 2023

Viruses

Self Cite

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Mitochondrial Spermidine Synthase is Essential for Blood-stage growth of the Malaria Parasite

Kamil

Kına

Deveci

et al. 2022

Microbiological Research

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The Quest for Immunity: Exploring Human Herpesviruses as Vaccine Vectors

Kamel,

Munds,

Verma

2023

IJMS

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Herpesviruses are large DNA viruses that have long been used as powerful gene therapy tools. In recent years, the ability of herpesviruses to stimulate both innate and adaptive immune responses has led to their transition to various applications as vaccine vectors. This vaccinology branch is growing at an unprecedented and accelerated rate. To date, human herpesvirus-based vectors have been used in vaccines to combat a variety of infectious agents, including the Ebola virus, foot and mouth disease virus, and human immunodeficiency viruses. Additionally, these vectors are being tested as potential vaccines for cancer-associated antigens. Thanks to advances in recombinant DNA technology, immunology, and genomics, numerous steps in vaccine development have been greatly improved. A better understanding of herpesvirus biology and the interactions between these viruses and the host cells will undoubtedly foster the use of herpesvirus-based vaccine vectors in clinical settings. To overcome the existing drawbacks of these vectors, ongoing research is needed to further advance our knowledge of herpesvirus biology and to develop safer and more effective vaccine vectors. Advanced molecular virology and cell biology techniques must be used to better understand the mechanisms by which herpesviruses manipulate host cells and how viral gene expression is regulated during infection. In this review, we cover the underlying molecular structure of herpesviruses and the strategies used to engineer their genomes to optimize capacity and efficacy as vaccine vectors. Also, we assess the available data on the successful application of herpesvirus-based vaccines for combating diseases such as viral infections and the potential drawbacks and alternative approaches to surmount them.

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An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge

Cited by 4 publications

References 14 publications

Inactivation of the UL37 Deamidase Enhances Virus Replication and Spread of the HSV-1(VC2) Oncolytic Vaccine Strain and Secretion of GM-CSF

Inactivation of the UL37 Deamidase Enhances Virus Replication and Spread of the HSV-1(VC2) Oncolytic Vaccine Strain and Secretion of GM-CSF

Mitochondrial Spermidine Synthase is Essential for Blood-stage growth of the Malaria Parasite

The Quest for Immunity: Exploring Human Herpesviruses as Vaccine Vectors

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