Vaccine-induced antibodies to the native, oligomeric envelope glycoproteins of primary HIV-1 isolates

Lee, Sandra A; Orque, Roland; Escarpe, Paul A.; Peterson, Michael; Good, Jeremy; Zaharias, Evanthia M; Berman, Phillip W.; Sheppard, Haynes W.; Shibata, Riri

doi:10.1016/s0264-410x(01)00334-6

Cited by 17 publications

(11 citation statements)

References 62 publications

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“…While the overall levels of Env-specific antibodies were low and not broadly cross-reactive, their binding specificity was measured against selected peptides of Env proteins rather than the primary Env antigens themselves [4,45]. Our results clearly demonstrate the benefit of delivering polyvalent Env antigens through the DNA prime-protein boost approach.…”

Section: Discussionmentioning

confidence: 72%

“…Serum and PBMC samples were collected at Study Weeks 0, 2,4,6,12,14,16,20,22,24,28,30,32,36 and 52 to measure antibody and CMI responses. All volunteers were recruited and enrolled in the Clinical Vaccine Research Unit, UMMS.…”

Section: 3b Study Design and Immunization Schedule-thismentioning

confidence: 99%

“…Early efforts in HIV vaccine development focused on the induction of humoral responses by using recombinant Env glycoproteins [2][3][4][5]. The immunogenicity of recombinant Env protein-based vaccines was poor in humans, as shown by overall low-level binding antibodies measured by solid phase assays [6] and by the narrow spectrum of neutralizing activities mainly against T-cell line adapted (TCLA) viral isolates [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

124

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An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6−001 in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNγ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cellmediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.

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Section: Discussionmentioning

confidence: 72%

Section: 3b Study Design and Immunization Schedule-thismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

124

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“…20,22 Studies using conformationally correct macrophage-tropic (R5-using) gp120/160 suggested that these reagents induced antibody recognizing native conformation and that these antibodies might be more broadly neutralizing. [35][36][37][38] Analogously, the use of oligomeric gp140/160, mimicking the native quaternary structure of the HIV envelope, might similarly induce NAb capable of neutralizing primary isolates. 20,21,[39][40][41] In this open-label trial we provide the first description of humoral responses in human volunteers induced by immunization with an R5-tropic CM235 gp120, alone or in combination with TCLA SF2 gp120.…”

Section: Discussionmentioning

confidence: 99%

Specific Antibody Responses to Vaccination with Bivalent CM235/SF2 gp120: Detection of Homologous and Heterologous Neutralizing Antibody to Subtype E (CRF01.AE) HIV Type 1

Kim

Pitisuttithum²,

C³

et al. 2003

AIDS Research and Human Retroviruses

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HIV-1 CRF.AE-01 (formerly subtype E) infection is highly prevalent in Southeast Asia. Despite success with public health measures, the development of an effective CRF01.AE vaccine is critical to the control of this epidemic. Sera from the open-label arms of the first clinical trial of a bivalent HIV gp120 SF2/CM235 (subtypes B and CRF.AE-01, respectively) vaccine were evaluated for the presence of gp120-specific binding (BAb) and neutralizing antibody (NAb). Twelve pre- and postvaccination sera pairs were tested for CM235 BAb; anti-gp120 CM235 BAb was found in all postvaccination samples. The 12 pre- and postvaccination (1 month after third vaccination) serum pairs were evaluated in several neutralization formats: heterologous T cell line adapted (TCLA) NP03/H9, homologous CM235/PBMC, CM235/dendritic cell, and CM235M4-C4.6/A3R5. A3R5 is a CCR5+ T cell line, and CM235M4-C4.6 is the homologous CM235 virus adapted to growth in A3R5 cells. All volunteers developed BAb, but meaningful NAb was not demonstrable against primary isolate CM235. Using the TCLA CRF01.AE virus NP03 in H9 cells, 9 of 12 persons had NAb with a geometric mean titer (GMT) of 46. The CM235M4-C4.6 virus in A3R5 cells also detected NAb in 9 of 12 persons, with a GMT of 41. CM235M4-C4.6/A3R5 detected NAb in two persons with negligible NAb to NP03/H9 and vice versa. Whether the NAb detected by the CM235M4-C4.6/A3R5 system is qualitatively different from those in more traditional NP03/H9 assays will require further study.

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“…Prior attempts using an Env glycoprotein-based vaccine design have been hampered either by poor immunogenicity (1) or by the lack of an antibody response that can effectively neutralize several circulating strains of HIV (56). This result may be due partly to the use of recombinant Env glycoproteins based on a single viral isolate (38,40,47,52,59). Attempts at vaccinating with recombinant viral vectors encoding Env glycoprotein and boosting with gp120 recombinant proteins have not been successful in generating broadly reactive antibodies capable of neutralizing primary viral isolates (35).…”

mentioning

confidence: 99%

Multifunctional T-Cell Characteristics Induced by a Polyvalent DNA Prime/Protein Boost Human Immunodeficiency Virus Type 1 Vaccine Regimen Given to Healthy Adults Are Dependent on the Route and Dose of Administration

Bansal

Jackson²,

West

et al. 2008

J Virol

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Vaccine-induced antibodies to the native, oligomeric envelope glycoproteins of primary HIV-1 isolates

Cited by 17 publications

References 62 publications

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Specific Antibody Responses to Vaccination with Bivalent CM235/SF2 gp120: Detection of Homologous and Heterologous Neutralizing Antibody to Subtype E (CRF01.AE) HIV Type 1

Multifunctional T-Cell Characteristics Induced by a Polyvalent DNA Prime/Protein Boost Human Immunodeficiency Virus Type 1 Vaccine Regimen Given to Healthy Adults Are Dependent on the Route and Dose of Administration

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