Abstract
Developing an effective HIV-1 vaccine will require strategies to enhance antigen presentation to the immune system. In a previous study we demonstrated a marked increase in immunogenicity of the highly glycosylated HIV-1 gp120 protein following enzymatic addition of α-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120αgal can also serve as an effective platform for targeting other HIV-1 proteins to APC and thus increase immunogenicity of both proteins. For this purpose we produced a recombinant fusion protein between gp120 and the HIV-1 matrix p24 protein (gp120/p24). Multiple α-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120αgal/p24 vaccine. Immune responses to gp120αgal/p24 compared to gp120/p24 vaccine lacking α-gal epitopes were evaluated in α1,3galactosyltransferase knockout (KO) mice. These mice lack α-gal epitopes and, therefore, are capable of producing the anti-Gal antibody. T cell responses to p24, as assessed by ELISPOT and by CD8+ T cells intracellular staining assays for IFNγ, was on average 12- and 10-fold higher, respectively, in gp120αgal/p24 immunized mice than in mice immunized with gp120/p24. In addition, cellular and humoral immune responses against gp120 were higher by 10-30-fold in mice immunized with gp120αgal/p24 than in gp120/p24 immunized mice. Our data suggest that the α-gal epitopes on the gp120 portion of the fusion protein can significantly augment the immunogenicity of gp120, as well as that of the fused viral protein which lacks α-gal epitopes. This strategy of anti-Gal mediated targeting to APC may be used for production of effective HIV-1 vaccines comprised of various viral proteins fused to gp120.
| Original language | English |
|---|---|
| Pages (from-to) | 1758-1765 |
| Number of pages | 8 |
| Journal | Vaccine |
| Volume | 28 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 17 Feb 2010 |
| Externally published | Yes |
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Keywords
- Alpha-gal epitopes
- HIV
- Immunogenicity
- Vaccine
ASJC Scopus subject areas
- Molecular Medicine
- Immunology and Microbiology(all)
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
Cite this
Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing α-gal epitopes. / Abdel-Motal, Ussama M.; Wang, Shixia; Awad, Amany; Lu, Shan; Wigglesworth, Kim; Galili, Uri.
In: Vaccine, Vol. 28, No. 7, 17.02.2010, p. 1758-1765.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing α-gal epitopes
AU - Abdel-Motal, Ussama M.
AU - Wang, Shixia
AU - Awad, Amany
AU - Lu, Shan
AU - Wigglesworth, Kim
AU - Galili, Uri
PY - 2010/2/17
Y1 - 2010/2/17
N2 - Developing an effective HIV-1 vaccine will require strategies to enhance antigen presentation to the immune system. In a previous study we demonstrated a marked increase in immunogenicity of the highly glycosylated HIV-1 gp120 protein following enzymatic addition of α-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120αgal can also serve as an effective platform for targeting other HIV-1 proteins to APC and thus increase immunogenicity of both proteins. For this purpose we produced a recombinant fusion protein between gp120 and the HIV-1 matrix p24 protein (gp120/p24). Multiple α-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120αgal/p24 vaccine. Immune responses to gp120αgal/p24 compared to gp120/p24 vaccine lacking α-gal epitopes were evaluated in α1,3galactosyltransferase knockout (KO) mice. These mice lack α-gal epitopes and, therefore, are capable of producing the anti-Gal antibody. T cell responses to p24, as assessed by ELISPOT and by CD8+ T cells intracellular staining assays for IFNγ, was on average 12- and 10-fold higher, respectively, in gp120αgal/p24 immunized mice than in mice immunized with gp120/p24. In addition, cellular and humoral immune responses against gp120 were higher by 10-30-fold in mice immunized with gp120αgal/p24 than in gp120/p24 immunized mice. Our data suggest that the α-gal epitopes on the gp120 portion of the fusion protein can significantly augment the immunogenicity of gp120, as well as that of the fused viral protein which lacks α-gal epitopes. This strategy of anti-Gal mediated targeting to APC may be used for production of effective HIV-1 vaccines comprised of various viral proteins fused to gp120.
AB - Developing an effective HIV-1 vaccine will require strategies to enhance antigen presentation to the immune system. In a previous study we demonstrated a marked increase in immunogenicity of the highly glycosylated HIV-1 gp120 protein following enzymatic addition of α-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120αgal can also serve as an effective platform for targeting other HIV-1 proteins to APC and thus increase immunogenicity of both proteins. For this purpose we produced a recombinant fusion protein between gp120 and the HIV-1 matrix p24 protein (gp120/p24). Multiple α-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120αgal/p24 vaccine. Immune responses to gp120αgal/p24 compared to gp120/p24 vaccine lacking α-gal epitopes were evaluated in α1,3galactosyltransferase knockout (KO) mice. These mice lack α-gal epitopes and, therefore, are capable of producing the anti-Gal antibody. T cell responses to p24, as assessed by ELISPOT and by CD8+ T cells intracellular staining assays for IFNγ, was on average 12- and 10-fold higher, respectively, in gp120αgal/p24 immunized mice than in mice immunized with gp120/p24. In addition, cellular and humoral immune responses against gp120 were higher by 10-30-fold in mice immunized with gp120αgal/p24 than in gp120/p24 immunized mice. Our data suggest that the α-gal epitopes on the gp120 portion of the fusion protein can significantly augment the immunogenicity of gp120, as well as that of the fused viral protein which lacks α-gal epitopes. This strategy of anti-Gal mediated targeting to APC may be used for production of effective HIV-1 vaccines comprised of various viral proteins fused to gp120.
KW - Alpha-gal epitopes
KW - HIV
KW - Immunogenicity
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=75249107663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75249107663&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2009.12.015
DO - 10.1016/j.vaccine.2009.12.015
M3 - Article
C2 - 20034607
AN - SCOPUS:75249107663
VL - 28
SP - 1758
EP - 1765
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 7
ER -