Anti-HIV-1 and anti-HBV immune responses in mice after parenteral and nasal co-administration of a multiantigenic formulation.
The cell-mediated immune response to HIV-1 is an essential element of the mechanisms for viral replication control. Currently, most of the vaccine candidates in clinical trials were developed to stimulate HIV-1-specific CD8+ cytotoxic (CTL) and CD4+ T helper (Th) lymphocytes. We have been working on a novel approach to develop a vaccine formulation for HIV-1 using a recombinant multiepitopic protein (named CR3), which comprises CTL and Th epitope-rich regions of HIV-1 from several subtype B isolates, co-inoculated with the hepatitis B virus surface (HBsAg) and core (HBcAg) antigens of the hepatitis B virus (HBV) as adjuvant. According to our studies in mice, the nasal-subcutaneous co-administration of this multiantigenic formulation induces a strong Th1-biased specific response against CR3, CD8+ T cells in mice spleen and IFN-gamma-secreting cells in mesenteric lymph nodes. Cross-reactive p24-specific IFN-gamma-secreting cells in spleen were also detected. Moreover, Nef-specific antibodies were elicited in mice sera which might avoid the toxic effects of this antigen. However, a marginal anti-CR3 antibody response was elicited in vaginal mucosa. Additionally, we observed anti-HBsAg and anti-HBcAg cellular and humoral responses. In this regard, our multiantigenic formulation might provide immunity against HBV as an additional benefic considering the high HIV-1-HBV co-infection rate reported worldwide.
Centro de Ingeniería Genética y Biotecnología (CIGB), Havana, Cuba. enrique.iglesias@cigb.edu.cu
Enrique
E
Iglesias
Daymir
D
García
Yamilka
Y
Carrazana
Julio C
JC
Aguilar
Aniel
A
Sánchez
Lariza
L
Gorobaya
Aracelys
A
Blanco
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000032:analysis; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006511:Hepatitis B Antigens / Q000008:administration & dosage / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000276:immunology*; D018928:Immunity, Mucosal; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D014621:Vagina / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D007371:Interferon-gamma