Improved NYVAC-based Vaccine Vectors

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Nov 19

PMID 22096477

Citations 41

Authors

Karen V Kibler

Carmen E Gomez

Beatriz Perdiguero

Shukmei Wong

Trung Huynh

Susan Holechek

William Arndt

Victoria Jimenez

Ruben Gonzalez-Sanz

Karen Denzler

Elias K Haddad

Ralf Wagner

Rafick P Sekaly

James Tartaglia

Giuseppe Pantaleo

Bertram L Jacobs

Mariano Esteban

Affiliations

Soon will be listed here.

Abstract

While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

Citing Articles

Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501Y Strain of SARS-CoV-2.

Kibler K, Szczerba M, Lake D, Roeder A, Rahman M, Hogue B Vaccines (Basel). 2022; 10(8).

PMID: 35893821 PMC: 9394475. DOI: 10.3390/vaccines10081172.

Intranasal immunization with a vaccinia virus vaccine vector expressing pre-fusion stabilized SARS-CoV-2 spike fully protected mice against lethal challenge with the heavily mutated mouse-adapted SARS2-N501Y strain of SARS-CoV-2.

Kibler K, Szczerba M, Lake D, Roeder A, Rahman M, Hogue B bioRxiv. 2021; .

PMID: 34909775 PMC: 8669842. DOI: 10.1101/2021.12.06.471483.

Optimization of translation enhancing element use to increase protein expression in a vaccinia virus system.

Richard Jr H, Minder S, Sidhu A, Juba A, Jancovich J, Jacobs B J Gen Virol. 2021; 102(8).

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TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice.

Godot V, Tcherakian C, Gil L, Cervera-Marzal I, Li G, Cheng L PLoS Pathog. 2020; 16(11):e1009025.

PMID: 33253297 PMC: 7728200. DOI: 10.1371/journal.ppat.1009025.

Repair of a previously uncharacterized second host-range gene contributes to full replication of modified vaccinia virus Ankara (MVA) in human cells.

Peng C, Moss B Proc Natl Acad Sci U S A. 2020; 117(7):3759-3767.

PMID: 32019881 PMC: 7035496. DOI: 10.1073/pnas.1921098117.

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