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Update on HIV Vaccine

Download presentation slides by Barney Graham, M.D., Ph.D.

 
Slide1: Components of a Vaccine

Slide1:
Components of a Vaccine

Vaccines depend on an antigenic component to provide specificity to the vaccine-induced immune response, but other qualities of vaccine-induced immunity depend on the formulation and delivery of the product.

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Slide 2: Vaccine-Induced Immunologic Mechanisms for Virus Clearance

Slide 2:
Vaccine-Induced Immunologic Mechanisms for Virus Clearance

Vaccine-induced immunity relies on components of the adaptive immune response. This slide illustrates how the virus proteins made for assembly of new virions are also processed and transported into compartments where selected peptides (epitopes) can interact with MHC molecules and then interact with T cells leading to activation and expansion. The slide can also be used to explain how important CD8+ T cells are for recognizing and killing virus-infected cells, how CD4 T cells produce cytokines that facilitate the growth and differentiation of other T cells and B cells, and antibodies are best able to recognize structures on the surface of viruses and virus-infected cells.

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Slide 3: The Role of Vaccine-Inducible Immune Responses to Different Phases of HIV Infection

Slide 3:
The Role of Vaccine-Inducible Immune Responses to Different Phases of HIV Infection

Antibody is the only component of the adaptive immune response that provides a defense against a cell-free virion, and T lymphocytes are the primary mechanisms in the adaptive immune response to clear virus-infected cells. The slide also can be used to explain the concept of viral latency and the problem of the viral reservoir in HIV infection.

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Slide 4: Timing of Vaccine-Induced Immune Responses

Slide 4:
Timing of Vaccine-Induced Immune Responses

There are several points to be made about the kinetics of early HIV infection, the concept of viral load "setpoint", or the dynamic equilibrium between virus production and virus clearance that is established during untreated HIV infection. The slide is also useful for making points about the concept that vaccine-induced immunity is the consequence of subtle changes in the kinetics and timing of the immune responses that can potentially have a large impact on disease expression.

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Slide 5: Potential Outcomes of HIV Infection in the Setting of Vaccine-Induced Immunity

Slide 5:
Potential Outcomes of HIV Infection in the Setting of Vaccine-Induced Immunity

Changes in the timing and magnitude of immune responses can have a major impact on the disease progression in HIV infection. The white line represents a typical virus load (or disease severity). The dashed green lines represent the hypothetical disease course or virus load in a person with prior vaccination and immunity that limits the peak of viremia and controls infection at a very low virus load, or eradicates all virus-infected cells preventing persistent infection most significantly in animal models where high levels of virus-specific CD8+ T cell responses have been induced with vaccine, the line representing controlled, but persistent infection has been achieved in some systems.

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Slide 6: Traditional Approaches to Vaccine Development

Slide 6:
Traditional Approaches to Vaccine Development

This slide is a representation of traditional whole virus vaccine approaches.

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Slide 7: Extraction of Viral RNA and Conversion to DNA

Slide 7:
Extraction of Viral RNA and Conversion to DNA

Slides seven through 9 illustrate the distinction between traditional vaccine approaches and those that use recombinant DNA technology for producing vaccine antigens and gene delivery vehicles. First RNA is extracted and converted into DNA using reverse transcription.

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Slide 8: Cloning a Gene into a Plasmid

Slide 8:
Cloning a Gene into a Plasmid

Selected regions of DNA that encode structural or antigenic domains of interest can be amplified using polymerase chain reaction (PCR), then cloned into bacterial plasmids.

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Slide 9: Growth and Purification of Plasmids

Slide 9:
Growth and Purification of Plasmids

Bacterial plasmids can easily be grown in large quantities and purified.

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Slide 10: Recombinant DNA Technology and Vaccine Development

Slide 10:
Recombinant DNA Technology and Vaccine Development

It is key to note that vaccines made with recombinant DNA technology do not use whole virus in the manufacturing process. The genes used to express the antigenic structure of interest are modified and resynthesized in the final product, so it is not possible for any of the vaccines being tested to cause HIV infection. The other major point to make is about the value of in vivo antigen production referring back to the concepts illustrated in slides 2, 3, and 4, and indicating that when the vaccine antigen is made inside the cell, there is a much more potent induction of the CD8+ T cell response, thought to be associated with control of HIV infection.

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Slide 11: Determinants of an Epidemic

Slide 11:
Determinants of an Epidemic

This formula is used to make two important points. First even if a vaccine is partially effective with respect to the outcome of infection in a single individual, if there is a reduction in the transmission efficiency or the duration of infectious period, the vaccine may have a large impact on the epidemic in a given population and second and perhaps more important is the role of the middle value "c". If risk-taking activities increase, the effectiveness of an imperfect vaccine can be undone. Therefore, risk-reduction counseling and education is important now, and will be important during vaccine trials, and will be important to continue even after a vaccine is licensed.

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