Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant

Article Abstract:

An effective vaccine against HIV-1 (human immunodeficiency virus type 1, which causes AIDS) has not yet been developed. Vaccine development has been hindered, in part, by variability in protein structure among different isolates of HIV-1. Moreover, the main target for antibodies that normally neutralize the infectivity of viruses, the viral protein coat, is particularly variable. The specific principal neutralizing determinant (PND) of HIV-1 lies within a protein known as gp120 in the viral protein coat (envelope). A consequence of its variability from one HIV-1 isolate to another, which may be as high as 50 percent, is that antibodies elicited by the PND from one isolate do not neutralize isolates with PNDs containing different amino acid sequences. A better vaccine could be made if more information were obtained regarding the most common PND sequences. To this end, the viral proteins in blood cells from 133 HIV-1-infected people were studied to determine the PND sequence in each. From these, 222 PND sequences were obtained, and data from other research reports added another 23 sequences. Analyses of these 245 sequences showed that the PND is actually less variable than previously thought. In fact, more than 80 percent of the amino acids in several positions in the PND appeared to be identical. Furthermore, specific sequences recurred in many isolates; this implies that an appropriately directed antibody could be expected to neutralize the majority of isolates. Vaccines should be developed based on viral isolates from representative HIV-1 strains, rather than from strains with rare PND sequences, such as the HTLV-IIIB or LAV-1 (BRU) isolates. Overall, the results suggest that a successful vaccine could be made using isolates with the most prevalent PND sequences. (Consumer Summary produced by Reliance Medical Information, Inc.)

HIV infection, HIV infections

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Progress in vaccines against AIDS

Article Abstract:

Although scientists were pessimistic about the development of a vaccine against HIV, the human immunodeficiency virus which causes AIDS, recent advances have made them optimistic. Animal studies using the simian immunodeficiency virus and the equine infectious anemia virus showed that vaccines made from whole killed virus delayed the onset of disease, perhaps permanently, even when the virus was still present in the body. Thus it may not be necessary to block virus infection to bring about immunity. Although the use of whole virus for vaccines is important for vaccine development, it is not practical for clinical use because of the possibility of the presence of infectious virus. Therefore, scientists have been looking for the molecules that are involved in the development of immunity. Several advances have been made in these studies. Molecules which are involved in the infectious process have been identified on both the virus and the T cells, a subset of lymphocytes to which the virus binds. Other advances have been made in the understanding of how the virus causes suppression of the immune system. It has been shown in tissue culture that antibodies can be produced that enhance rather than prevent infection. However, these enhancing antibodies have not been seen in the animal models, nor in humans immunized with virus antigens. Although these recent advances are important, there are many other obstacles to overcome before a vaccine to AIDS will be available. With more research, these problems will hopefully be solved as well. (Consumer Summary produced by Reliance Medical Information, Inc.)

AIDS (Disease)

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Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1

Article Abstract:

Antibodies that are made against a certain region, known as the principal neutralizing determinant (PND), of the envelope (outer coat) protein of the human immunodeficiency virus type-1 (HIV-1) neutralize the virus, or make it inactive. Antibodies specific to this region can neutralize various isolates of HIV that are structurally different from each other. Peptides, identical to those in this region, of the human T cell lymphoma virus (HTLV) of the type IIIMN, were synthesized in the laboratory and used to immunize animals. Antibodies from one out of three animals immunized were able to neutralize the HTLV-IIIMN virus and also a different virus, HTLV-IIIB. The peptide that was being recognized by the antibody was characterized and was found to be similar to a peptide also found in more than half of the HIV-1 isolates. It may be possible that antibodies can be made against this peptide and be given to patients who are infected with HIV or HTLV to neutralize the virus and prevent it from causing an infection. Even more promising is that vaccines can be made with this peptide that could stimulate an immune response to neutralize the viruses. (Consumer Summary produced by Reliance Medical Information, Inc.)

HTLV (Viruses), HTLV viruses, HIV antibodies

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