ABSTRACT
We have recently developed a candidate HIV-1 vaccine based on virus-like particles (VLPs) expressing a gp120 from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). In vivo immunogenicity experiments were performed in Balb/c mice, with an immunization schedule based on a multiple-dose regimen of HIV-VLP(A)s without adjuvants, showing a significant induction of both humoral and cellular immunity. The Env-specific cellular response was investigated in vitro, scoring for both the proliferative response of T helper cells and the cytolytic activity of cytotoxic T lymphocytes (CTLs). Furthermore, immune sera showed >50% neutralization activity against both the autologous field isolate and the heterologous T cell adapted B-clade HIV-1(IIIB) viral strain. This is one of the first examples of HIV-1 vaccines based on antigens derived from the A clade, which represents >25% of all isolates identified world wide. In particular, the A clade is predominant in sub-Saharan countries, where 70% of the global HIV-1 infections occur, and where vaccination is the only rational strategy for an affordable prevention against HIV-1 infection.
Subject(s)
AIDS Vaccines/immunology , HIV Envelope Protein gp120/immunology , HIV Infections/immunology , HIV-1/immunology , T-Lymphocytes, Cytotoxic/immunology , AIDS Vaccines/therapeutic use , Animals , Antibodies, Viral/biosynthesis , Antibodies, Viral/blood , Baculoviridae/genetics , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , HIV Infections/prevention & control , HIV-1/genetics , Humans , Immunization , Male , Mice , Mice, Inbred BALB C , Neutralization Tests , Recombinant Proteins/genetics , Recombinant Proteins/immunology , T-Lymphocytes, Helper-Inducer/immunologyABSTRACT
"In order to identify HIV-1 strains prevalent in Northern Uganda; peripheral blood mononuclear cells (PBMC) of 19 asympotomatic seropositive pregnant women from the District of Gulu-Northern Uganda have been analysed. A 700bp fragment of the HIV-1 env gene; including the V3-V5 region; amplified by Polymerase chain Reaction (PCR) from 10 samples (52.6); was subjected to both heteroduplex Mobility Assay (HMA); for genetic subtyping; and DNA sequence analysis; for nucleotide comparison and phylogenetic studies. The results show the presence of HIV-1 ""A"" and ""D"" subtypes/clades with a strong prevalence; in this rural area; of the ""A""(8/10) over the ""D"" subtype (2/10) unlike what was previously reported in Uganda. By pairwise comparison analysis; the percentage of sequence divergence is low among samples within each subtype (average inter-subtypes divergence of 23). At the aminoacidic level; the two HIV-1 groups are clearly distinct by a tetrameric GPGQ sequence at the V3 loop apex for the A and a GPGR sequence for the D clade. In addition; 10 out of the 19 viral samples (52.6) have been isolated in vitro and 9 of them have been classified as Rapid/High (R/H); showing the high in vitro replication capacity to field isolated also when obtained from asymptomatic individuals. These data; even though on a limited sample size; suggest that in Uganda HIV-1 isolates can be prevalently grouped in 2 major clades; and the comparison of Gulu HIV-1 sequences with the two consensus sequences (Group A and B) identified by Albert et al 1990; indicates that in a 4-year period no major genetic shifts have occurred. These results should be extremely relevant for Uganda future HIV-1 vaccine programs. Supported by Ministero Italiano Sanita (Ric.Corr.1994) and ISDC-World Laboratory; Lausanne (Project MCD-2/7)."
