Vaccines for the prevention of HIV-1 disease

Mascola, John R.; Nabel, Gary J.

doi:10.1016/s0952-7915(00)00246-6

Cited by 58 publications

(33 citation statements)

References 72 publications

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“…A major obstacle for effective antibody-based immunization against HIV-1 is viral diversity (8,19,38). To be effective, an HIV-1 vaccine will likely have to generate antibodies that neutralize a genetically and antigenically diverse set of viruses.…”

Section: Cd8mentioning

confidence: 99%

Recommendations for the Design and Use of Standard Virus Panels To Assess Neutralizing Antibody Responses Elicited by Candidate Human Immunodeficiency Virus Type 1 Vaccines

Mascola

DʼSouza

Gilbert

et al. 2005

J Virol

230

233

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Section: Cd8mentioning

confidence: 99%

Recommendations for the Design and Use of Standard Virus Panels To Assess Neutralizing Antibody Responses Elicited by Candidate Human Immunodeficiency Virus Type 1 Vaccines

Mascola

DʼSouza

Gilbert

et al. 2005

J Virol

230

233

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“…Despite limited expression of Ag in situ, impressive results have recently been obtained for DNA vaccines that are capable of priming the immune system more efficiently, resulting in highly boostable HIV-specific CD8 ϩ T cell responses in mice and rhesus macaques (7)(8)(9)(10)(11)(12)(13). As sentinels of the immune system, DC are at the crossroads of innate and adaptive immunity and therefore perform crucial roles in linking them functionally for immune augmentation.…”

Section: Long-term Maintenance Of Gp120-specific Immune Responses By mentioning

confidence: 99%

Long-Term Maintenance of gp120-Specific Immune Responses by Genetic Vaccination with the HIV-1 Envelope Genes Linked to the Gene Encoding Flt-3 Ligand

Gangadhara

Husain

Nayak

et al. 2003

The Journal of Immunology

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DNA vaccines target dendritic cells (DC) to induce Ag-specific immune responses in animals. Potent HIV-specific immunity could be achieved by efficient priming of the immune system by DNA vaccines. We investigated a novel DNA vaccine approach based on the role of growth factors in DC expansion and differentiation. To this end, we constructed chimeric genes encoding the HIV envelope glycoproteins physically linked to the extracellular domain of Fms-like tyrosine kinase receptor-3 ligand (FLex; a DC growth factor; both mouse (m)FLex and human (h)FLex). These chimeric gene constructs synthesized biologically active, oligomeric FLex:gp120 fusion proteins and induced DC expansion (CD11c+CD11b+) when injected i.v. into mice. This DC expansion is comparable to that achieved by FLex DNA encoding native FLex protein. When delivered intramuscularly as DNA vaccines, hFLex:gp120 induced high frequencies of gp120-specific CD8+ T cells in the presence or absence of FLex DNA-induced DC expansion, but gp120 and mFLex:gp120 elicited only low to moderate levels of Ag-specific CD8+ T cells. In contrast, mFLex:gp120 induced high levels of anti-gp120 Abs under identical conditions of DNA vaccination. However, the Ab levels in mice immunized with DNA vaccines encoding hFLex:gp120 and gp120 proteins were low without DC expansion, but reached high levels comparable to that elicited by mFLex:gp120 only after the second boost in the presence of DC expansion. Importantly, the gp120-specific CD8+ T cells persisted at high frequency for 114 days (16 wk) after a booster injection. These experiments provide insight into the importance of modulating DC function in vivo for effective genetic vaccination in animals.

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“…However, efforts to develop an Env-based immunogen that elicits an effective neutralizing antibody response are hampered by the high mutation rate of the virus in infected individuals (23) and the resulting genetic heterogeneity and structural complexity exhibited by Env (24). Thus, an effective HIV-1 vaccine will need to target a plethora of genetic and antigenic variants of the virus.A variety of candidate HIV-1 vaccines have included Env for the purpose of generating a neutralizing antibody response (8,14,20). Among these, DNA vaccines have proven to be poor inducers of neutralizing antibodies on their own but nonetheless prime for a detectable neutralizing antibody response after Env protein boosting (1,9,11,13,21,22).…”

mentioning

confidence: 99%

“…A variety of candidate HIV-1 vaccines have included Env for the purpose of generating a neutralizing antibody response (8,14,20). Among these, DNA vaccines have proven to be poor inducers of neutralizing antibodies on their own but nonetheless prime for a detectable neutralizing antibody response after Env protein boosting (1,9,11,13,21,22).…”

mentioning

confidence: 99%

Enhanced Immunogenicity of gp120 Protein When Combined with Recombinant DNA Priming To Generate Antibodies That Neutralize the JR-FL Primary Isolate of Human Immunodeficiency Virus Type 1

Wang

Arthos

Lawrence

et al. 2005

J Virol

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Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a strategy to generate neutralizing antibodies. Both plasmidbased and recombinant protein envelope (Env) glycoprotein immunogens were derived from a primary viral isolate, JR-FL. Serum from rabbits immunized with either gp120 or gp140 DNA vaccines delivered by gene gun inoculation followed by recombinant gp120 protein boosting was capable of neutralizing JR-FL. Neither the DNA vaccines alone nor the gp120 protein alone generated a detectable neutralizing antibody response against this virus. Neutralizing antibody responses using gp120 DNA and gp140 DNA for priming were similar. The results suggest that Env DNA priming followed by gp120 protein boosting provides an advantage over either approach alone for generating a detectable neutralizing antibody response against primary isolates that are not easily neutralized.Neutralizing antibodies are considered critical immune components for effective vaccination against human immunodeficiency virus type 1 (HIV-1) infection and disease (5,10,16,19). The HIV-1 envelope glycoproteins (Env) are the primary viral antigens targeted by neutralizing antibodies. However, efforts to develop an Env-based immunogen that elicits an effective neutralizing antibody response are hampered by the high mutation rate of the virus in infected individuals (23) and the resulting genetic heterogeneity and structural complexity exhibited by Env (24). Thus, an effective HIV-1 vaccine will need to target a plethora of genetic and antigenic variants of the virus.A variety of candidate HIV-1 vaccines have included Env for the purpose of generating a neutralizing antibody response (8,14,20). Among these, DNA vaccines have proven to be poor inducers of neutralizing antibodies on their own but nonetheless prime for a detectable neutralizing antibody response after Env protein boosting (1,9,11,13,21,22). Unfortunately, the neutralizing antibodies generated in these studies have primarily targeted T-cell-line-adapted strains and a small fraction of primary isolates of HIV-1 that are unusually sensitive to neutralization. Most primary isolates of HIV-1 are substantially less sensitive to neutralization and more difficult to target with vaccines (2-4, 15).It has not been clear whether the DNA prime and protein boost strategy affords an advantage over Env protein immunization alone with respect to the elicitation of a neutralizing antibody response that targets typical primary HIV-1 isolates that are not easily neutralized. In this regard, the JR-FL strain of HIV-1 exhibits such a neutralization phenotype (6) and therefore represents a relevant viral target upon which different vaccine strategies can be evaluated and compared. In the present study, we investigated the ability of the JR-FL gp120 protein to generate a neutralizing antibody response with and with...

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Vaccines for the prevention of HIV-1 disease

Cited by 58 publications

References 72 publications

Recommendations for the Design and Use of Standard Virus Panels To Assess Neutralizing Antibody Responses Elicited by Candidate Human Immunodeficiency Virus Type 1 Vaccines

Recommendations for the Design and Use of Standard Virus Panels To Assess Neutralizing Antibody Responses Elicited by Candidate Human Immunodeficiency Virus Type 1 Vaccines

Long-Term Maintenance of gp120-Specific Immune Responses by Genetic Vaccination with the HIV-1 Envelope Genes Linked to the Gene Encoding Flt-3 Ligand

Enhanced Immunogenicity of gp120 Protein When Combined with Recombinant DNA Priming To Generate Antibodies That Neutralize the JR-FL Primary Isolate of Human Immunodeficiency Virus Type 1

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