Alphavirus replicon particles as candidate HIV vaccines

Nancy L. Davis, Ande West, Elizabeth Reap, Gene MacDonald, Martha Collier, Sergey Dryga, Maureen Maughan, Mary Connell, Chris Walker, Kathryn McGrath, Chad Cecil, Li Hua Ping, Jeffrey A Frelinger, Robert Olmsted, Paula Keith, Ronald Swanstrom, Carolyn Williamson, Philip Johnson, David Montefiori, Robert E. Johnston

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of replicon RNA into VEE replicon particles (VRPs) are expressed from separate helper RNAs. Aspects of the biology of VEE that are exploited in VRP vaccines include 1) expression of very high levels of immunogen, 2) expression of immunizing proteins in cells in the draining lymph node, and 3) the ability to induce mucosal immunity from a parental inoculation. Results of experiments with VRPs expressing green fluorescent protein or influenza virus hemagglutinin (HA) demonstrated that specific mutations in the VRP envelope glycoproteins affect both targeting in the draining lymph node and efficiency of the immune response in mice. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIV sm H-4i were mixed in a cocktail and used to immunize macaques at 0, 1, and 4 months. Neutralizing antibodies against SIV sm H-4 were induced in 6 of 6 vaccinates and CTL in 4 of 6. An intrarectal challenge with the highly pathogenic SIV sm E660 was given at 5 months. A vaccine effect was seen in reduced peak virus loads, reduced virus loads both at set point and at 41 weeks postchallenge, and preserved or increased CD4 counts compared to controls. A candidate VRP HIV vaccine expressing Clade C Gag contains a sequence that is very close to the South African Clade C consensus and was selected from a recent seroconverter in the Durban cohort to represent currently circulating genotypes in South Africa. A GMP lot of this vaccine has been manufactured and tested for a phase I trial in the first months of 2002.

Original languageEnglish (US)
Pages (from-to)209-211
Number of pages3
JournalIUBMB Life
Volume53
Issue number4-5
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Alphavirus
AIDS Vaccines
Replicon
Viruses
Venezuelan Equine Encephalitis Viruses
Vaccines
RNA
Genes
Lymph Nodes
Viral Structural Proteins
Mucosal Immunity
Proteins
Capsid
Hemagglutinins
Macaca
Product Packaging
CD4 Lymphocyte Count
South Africa
Green Fluorescent Proteins
Neutralizing Antibodies

Keywords

  • Dendritic cell targeting in vivo
  • Mucosal SIV challenge in macaques
  • SIV sm E660 intrarectal challenge
  • Venezuelan equine encephalitis virus replicon particles

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Davis, N. L., West, A., Reap, E., MacDonald, G., Collier, M., Dryga, S., ... Johnston, R. E. (2002). Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life, 53(4-5), 209-211. https://doi.org/10.1080/15216540212657

Alphavirus replicon particles as candidate HIV vaccines. / Davis, Nancy L.; West, Ande; Reap, Elizabeth; MacDonald, Gene; Collier, Martha; Dryga, Sergey; Maughan, Maureen; Connell, Mary; Walker, Chris; McGrath, Kathryn; Cecil, Chad; Ping, Li Hua; Frelinger, Jeffrey A; Olmsted, Robert; Keith, Paula; Swanstrom, Ronald; Williamson, Carolyn; Johnson, Philip; Montefiori, David; Johnston, Robert E.

In: IUBMB Life, Vol. 53, No. 4-5, 2002, p. 209-211.

Research output: Contribution to journalArticle

Davis, NL, West, A, Reap, E, MacDonald, G, Collier, M, Dryga, S, Maughan, M, Connell, M, Walker, C, McGrath, K, Cecil, C, Ping, LH, Frelinger, JA, Olmsted, R, Keith, P, Swanstrom, R, Williamson, C, Johnson, P, Montefiori, D & Johnston, RE 2002, 'Alphavirus replicon particles as candidate HIV vaccines', IUBMB Life, vol. 53, no. 4-5, pp. 209-211. https://doi.org/10.1080/15216540212657
Davis NL, West A, Reap E, MacDonald G, Collier M, Dryga S et al. Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life. 2002;53(4-5):209-211. https://doi.org/10.1080/15216540212657
Davis, Nancy L. ; West, Ande ; Reap, Elizabeth ; MacDonald, Gene ; Collier, Martha ; Dryga, Sergey ; Maughan, Maureen ; Connell, Mary ; Walker, Chris ; McGrath, Kathryn ; Cecil, Chad ; Ping, Li Hua ; Frelinger, Jeffrey A ; Olmsted, Robert ; Keith, Paula ; Swanstrom, Ronald ; Williamson, Carolyn ; Johnson, Philip ; Montefiori, David ; Johnston, Robert E. / Alphavirus replicon particles as candidate HIV vaccines. In: IUBMB Life. 2002 ; Vol. 53, No. 4-5. pp. 209-211.
@article{3f69fd39074947dfb5f004e5aaac415c,
title = "Alphavirus replicon particles as candidate HIV vaccines",
abstract = "Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of replicon RNA into VEE replicon particles (VRPs) are expressed from separate helper RNAs. Aspects of the biology of VEE that are exploited in VRP vaccines include 1) expression of very high levels of immunogen, 2) expression of immunizing proteins in cells in the draining lymph node, and 3) the ability to induce mucosal immunity from a parental inoculation. Results of experiments with VRPs expressing green fluorescent protein or influenza virus hemagglutinin (HA) demonstrated that specific mutations in the VRP envelope glycoproteins affect both targeting in the draining lymph node and efficiency of the immune response in mice. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIV sm H-4i were mixed in a cocktail and used to immunize macaques at 0, 1, and 4 months. Neutralizing antibodies against SIV sm H-4 were induced in 6 of 6 vaccinates and CTL in 4 of 6. An intrarectal challenge with the highly pathogenic SIV sm E660 was given at 5 months. A vaccine effect was seen in reduced peak virus loads, reduced virus loads both at set point and at 41 weeks postchallenge, and preserved or increased CD4 counts compared to controls. A candidate VRP HIV vaccine expressing Clade C Gag contains a sequence that is very close to the South African Clade C consensus and was selected from a recent seroconverter in the Durban cohort to represent currently circulating genotypes in South Africa. A GMP lot of this vaccine has been manufactured and tested for a phase I trial in the first months of 2002.",
keywords = "Dendritic cell targeting in vivo, Mucosal SIV challenge in macaques, SIV sm E660 intrarectal challenge, Venezuelan equine encephalitis virus replicon particles",
author = "Davis, {Nancy L.} and Ande West and Elizabeth Reap and Gene MacDonald and Martha Collier and Sergey Dryga and Maureen Maughan and Mary Connell and Chris Walker and Kathryn McGrath and Chad Cecil and Ping, {Li Hua} and Frelinger, {Jeffrey A} and Robert Olmsted and Paula Keith and Ronald Swanstrom and Carolyn Williamson and Philip Johnson and David Montefiori and Johnston, {Robert E.}",
year = "2002",
doi = "10.1080/15216540212657",
language = "English (US)",
volume = "53",
pages = "209--211",
journal = "IUBMB Life",
issn = "1521-6543",
publisher = "Wiley-Blackwell",
number = "4-5",

}

TY - JOUR

T1 - Alphavirus replicon particles as candidate HIV vaccines

AU - Davis, Nancy L.

AU - West, Ande

AU - Reap, Elizabeth

AU - MacDonald, Gene

AU - Collier, Martha

AU - Dryga, Sergey

AU - Maughan, Maureen

AU - Connell, Mary

AU - Walker, Chris

AU - McGrath, Kathryn

AU - Cecil, Chad

AU - Ping, Li Hua

AU - Frelinger, Jeffrey A

AU - Olmsted, Robert

AU - Keith, Paula

AU - Swanstrom, Ronald

AU - Williamson, Carolyn

AU - Johnson, Philip

AU - Montefiori, David

AU - Johnston, Robert E.

PY - 2002

Y1 - 2002

N2 - Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of replicon RNA into VEE replicon particles (VRPs) are expressed from separate helper RNAs. Aspects of the biology of VEE that are exploited in VRP vaccines include 1) expression of very high levels of immunogen, 2) expression of immunizing proteins in cells in the draining lymph node, and 3) the ability to induce mucosal immunity from a parental inoculation. Results of experiments with VRPs expressing green fluorescent protein or influenza virus hemagglutinin (HA) demonstrated that specific mutations in the VRP envelope glycoproteins affect both targeting in the draining lymph node and efficiency of the immune response in mice. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIV sm H-4i were mixed in a cocktail and used to immunize macaques at 0, 1, and 4 months. Neutralizing antibodies against SIV sm H-4 were induced in 6 of 6 vaccinates and CTL in 4 of 6. An intrarectal challenge with the highly pathogenic SIV sm E660 was given at 5 months. A vaccine effect was seen in reduced peak virus loads, reduced virus loads both at set point and at 41 weeks postchallenge, and preserved or increased CD4 counts compared to controls. A candidate VRP HIV vaccine expressing Clade C Gag contains a sequence that is very close to the South African Clade C consensus and was selected from a recent seroconverter in the Durban cohort to represent currently circulating genotypes in South Africa. A GMP lot of this vaccine has been manufactured and tested for a phase I trial in the first months of 2002.

AB - Replicon particles based on Venezuelan equine encephalitis virus (VEE) contain a self-replicating RNA encoding the VEE replicase proteins and expressing a gene of interest in place of the viral structural protein genes. Structural proteins for packaging of replicon RNA into VEE replicon particles (VRPs) are expressed from separate helper RNAs. Aspects of the biology of VEE that are exploited in VRP vaccines include 1) expression of very high levels of immunogen, 2) expression of immunizing proteins in cells in the draining lymph node, and 3) the ability to induce mucosal immunity from a parental inoculation. Results of experiments with VRPs expressing green fluorescent protein or influenza virus hemagglutinin (HA) demonstrated that specific mutations in the VRP envelope glycoproteins affect both targeting in the draining lymph node and efficiency of the immune response in mice. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIV sm H-4i were mixed in a cocktail and used to immunize macaques at 0, 1, and 4 months. Neutralizing antibodies against SIV sm H-4 were induced in 6 of 6 vaccinates and CTL in 4 of 6. An intrarectal challenge with the highly pathogenic SIV sm E660 was given at 5 months. A vaccine effect was seen in reduced peak virus loads, reduced virus loads both at set point and at 41 weeks postchallenge, and preserved or increased CD4 counts compared to controls. A candidate VRP HIV vaccine expressing Clade C Gag contains a sequence that is very close to the South African Clade C consensus and was selected from a recent seroconverter in the Durban cohort to represent currently circulating genotypes in South Africa. A GMP lot of this vaccine has been manufactured and tested for a phase I trial in the first months of 2002.

KW - Dendritic cell targeting in vivo

KW - Mucosal SIV challenge in macaques

KW - SIV sm E660 intrarectal challenge

KW - Venezuelan equine encephalitis virus replicon particles

UR - http://www.scopus.com/inward/record.url?scp=0035991717&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035991717&partnerID=8YFLogxK

U2 - 10.1080/15216540212657

DO - 10.1080/15216540212657

M3 - Article

C2 - 12120997

AN - SCOPUS:0035991717

VL - 53

SP - 209

EP - 211

JO - IUBMB Life

JF - IUBMB Life

SN - 1521-6543

IS - 4-5

ER -