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Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing alpha-gal epitopes.
Vaccine. 2010 Feb 17; 28(7):1758-65.V

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 alpha-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120(alphagal) 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 alpha-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120(alphagal)/p24 vaccine. Immune responses to gp120(alphagal)/p24 compared to gp120/p24 vaccine lacking alpha-gal epitopes were evaluated in alpha1,3galactosyltransferase knockout (KO) mice. These mice lack alpha-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 IFNgamma, was on average 12- and 10-fold higher, respectively, in gp120(alphagal)/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 gp120(alphagal)/p24 than in gp120/p24 immunized mice. Our data suggest that the alpha-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 alpha-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.

Authors+Show Affiliations

Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA. Ussama_abdel-motal@dfci.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20034607

Citation

Abdel-Motal, Ussama M., et al. "Increased Immunogenicity of HIV-1 P24 and Gp120 Following Immunization With Gp120/p24 Fusion Protein Vaccine Expressing Alpha-gal Epitopes." Vaccine, vol. 28, no. 7, 2010, pp. 1758-65.
Abdel-Motal UM, Wang S, Awad A, et al. Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing alpha-gal epitopes. Vaccine. 2010;28(7):1758-65.
Abdel-Motal, U. M., Wang, S., Awad, A., Lu, S., Wigglesworth, K., & Galili, U. (2010). Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing alpha-gal epitopes. Vaccine, 28(7), 1758-65. https://doi.org/10.1016/j.vaccine.2009.12.015
Abdel-Motal UM, et al. Increased Immunogenicity of HIV-1 P24 and Gp120 Following Immunization With Gp120/p24 Fusion Protein Vaccine Expressing Alpha-gal Epitopes. Vaccine. 2010 Feb 17;28(7):1758-65. PubMed PMID: 20034607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing alpha-gal epitopes. AU - Abdel-Motal,Ussama M, AU - Wang,Shixia, AU - Awad,Amany, AU - Lu,Shan, AU - Wigglesworth,Kim, AU - Galili,Uri, Y1 - 2009/12/22/ PY - 2009/08/17/received PY - 2009/11/23/revised PY - 2009/12/09/accepted PY - 2009/12/26/entrez PY - 2009/12/26/pubmed PY - 2010/4/14/medline SP - 1758 EP - 65 JF - Vaccine JO - Vaccine VL - 28 IS - 7 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 alpha-gal epitopes to the carbohydrate chains. In the present study we determined whether gp120(alphagal) 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 alpha-gal epitopes were synthesized enzymatically on the gp120 portion of the fusion protein to generate a gp120(alphagal)/p24 vaccine. Immune responses to gp120(alphagal)/p24 compared to gp120/p24 vaccine lacking alpha-gal epitopes were evaluated in alpha1,3galactosyltransferase knockout (KO) mice. These mice lack alpha-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 IFNgamma, was on average 12- and 10-fold higher, respectively, in gp120(alphagal)/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 gp120(alphagal)/p24 than in gp120/p24 immunized mice. Our data suggest that the alpha-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 alpha-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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/20034607/Increased_immunogenicity_of_HIV_1_p24_and_gp120_following_immunization_with_gp120/p24_fusion_protein_vaccine_expressing_alpha_gal_epitopes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(09)01919-7 DB - PRIME DP - Unbound Medicine ER -