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Chapter 20 : The Dilemma of Developing and Testing AIDS Vaccines

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Abstract:

This chapter discusses about an effective vaccine against human immunodeficiency virus (HIV). From the standpoint of vaccine development, it is becoming more and more apparent that HIV is like no other virus. Key features that have led to successful vaccines with other viruses appear to be missing and are replaced by ones that are not conducive to vaccine development. In the absence of natural immunity, one must confront several serious obstacles: (i) correlates of immunity become difficult to establish, (ii) the rationale for live attenuated or even whole inactivate vaccines is weakened because of concerns for safety, (iii) the specter that all immune responses to the pathogen may not necessarily be salutary must be resolved, and (iv) the need to better understand virulence and how to overcome it becomes paramount. Thus, the empiricism that historically has been so dominant in development of vaccines against viruses gives way to a concerted effort to understand the fine details of infection and pathogenesis and how these are balanced with the ensuing host responses. When faced with such obstacles, vaccine developers have sometimes turned to animal models. Several independent studies had demonstrated that recombinant envelope products were effective in preventing HIV infection in chimpanzees and that antibodies were the best correlate of protection. In any event, it is now evident that a great deal of momentum is required to drive an HIV vaccine to the all-important milestone of an efficacy trial. The chapter ends with Howard Temin's contribution to work on HIV vaccines.

Citation: Bolognesi D. 1995. The Dilemma of Developing and Testing AIDS Vaccines, p 301-312. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch20

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Figures

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Figure 1

Relative vaccine efficacy in nonhuman primates infected with SIV, HIV-2, and HIV-1 suggests that viral pathogenesis and virulence correlate inversely with ease of vaccination.

Citation: Bolognesi D. 1995. The Dilemma of Developing and Testing AIDS Vaccines, p 301-312. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch20
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Figure 2

Neutralization of laboratory strains versus primary isolates. Bars indicate the range of neutralization titers of sera from HIV-l-infected individuals and uninfected volunteers who were vaccinated with MN and SF-2 envelope glycoproteins performed with laboratory isolates grown on T-ceil lines (MN, SF-2) (A) and primary isolates (panel of 10) representative of clade B (origin of MN and SF-2) passaged only on PBMCs (B). Note that sensitivity of primary isolates to neutralization is much lower with both HIV-positive sera and sera from vaccines, but while a fraction of sera from HIV-1-infected individuals can still neutralize some of the isolates, none of the vaccinee sera tested registered positive readings. The minimum positive reading in our assay systems was a titer of 1:10.

Citation: Bolognesi D. 1995. The Dilemma of Developing and Testing AIDS Vaccines, p 301-312. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch20
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Figure 3

Model for structural transition in the HIV-1 TM protein leading lo an active fusogenic attack complex. A model that indicates a structural transition from a native oligomer to a fusogenic state following a trigger event (possibly gpl20 binding to CD4) is proposed. Features include (i) a native state held together by noncovalent protein-protein interactions to form the heterodimer of gp 120/41 and other interactions, principally through gp4l interactive sites (DP-178 and DP-107). to form homo-oligomers on the virus surfaces of the gp 120/41 complexes; (ii) shielding of the hydrophobic fusogenic peptide at the N terminus (F) in the native state; and (iii) a leucine zipper domain (DP-107) that exists as a homo-oligomer coiled coil only in the fusogenic state. When triggered, the fusion complex is generated through formation of coiled-coil interactions in homologous DP-107 domains, resulting in an extended α-helix similar to that in the model for influenza. This conformational change positions the fusion peptide for interaction with the cell membrane.

Citation: Bolognesi D. 1995. The Dilemma of Developing and Testing AIDS Vaccines, p 301-312. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch20
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References

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Tables

Generic image for table
Table 1

Guidelines for entry into efficacy trials

v Meets criteria; vv exceeds criteria; ?, not determined; x, fails to meet criteria based on virus neutralization in vitro.

Citation: Bolognesi D. 1995. The Dilemma of Developing and Testing AIDS Vaccines, p 301-312. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch20
Generic image for table
Table 2

HIV vaccine candidates in development

For review, see reference .

VLP, nucleic acid-free, noninfectious, viruslike particles that self-assemble in yeast, insect, and mammalian expression systems involving , and gene products of HIV.

Nonreplicating multiply mutated HIV.

Immunogenic protein sequences from other organisms coupled to HIV proteins or peptides.

Citation: Bolognesi D. 1995. The Dilemma of Developing and Testing AIDS Vaccines, p 301-312. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch20

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