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Questions and Answers
What is a primary advantage of peptide vaccines compared to protein-containing subunit vaccines?
What is a primary advantage of peptide vaccines compared to protein-containing subunit vaccines?
What is a notable characteristic of DNA vaccines compared to traditional methods of vaccine production?
What is a notable characteristic of DNA vaccines compared to traditional methods of vaccine production?
What immune response is primarily generated by the expression of antigenic protein within the APCs through DNA vaccines?
What immune response is primarily generated by the expression of antigenic protein within the APCs through DNA vaccines?
What issue is commonly encountered in the application of DNA vaccines in humans, despite successful animal models?
What issue is commonly encountered in the application of DNA vaccines in humans, despite successful animal models?
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Why are adjuvants often used in combination with DNA vaccines?
Why are adjuvants often used in combination with DNA vaccines?
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What was a significant finding from the clinical trial of an antimalarial DNA vaccine?
What was a significant finding from the clinical trial of an antimalarial DNA vaccine?
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What does the process of antigen gene expression within APCs allow for in DNA vaccines?
What does the process of antigen gene expression within APCs allow for in DNA vaccines?
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What is a challenge with using peptides for B cell stimulation?
What is a challenge with using peptides for B cell stimulation?
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What is the primary role of adjuvants in subunit vaccines?
What is the primary role of adjuvants in subunit vaccines?
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Why do polysaccharide vaccines require carrier proteins?
Why do polysaccharide vaccines require carrier proteins?
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What is a significant advantage of live, attenuated vaccines over killed vaccines?
What is a significant advantage of live, attenuated vaccines over killed vaccines?
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Which feature of the hepatitis B surface antigen is utilized to enhance vaccine effectiveness?
Which feature of the hepatitis B surface antigen is utilized to enhance vaccine effectiveness?
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What was the outcome of replacing L-alanine with L-threonine in synthetic adjuvant design?
What was the outcome of replacing L-alanine with L-threonine in synthetic adjuvant design?
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How do adjuvants like monophosphoryl lipid A function?
How do adjuvants like monophosphoryl lipid A function?
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What characteristic of whole pathogens contributes to their stronger immune response compared to pure subunit vaccines?
What characteristic of whole pathogens contributes to their stronger immune response compared to pure subunit vaccines?
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What is the main purpose of using recombinant DNA techniques in vaccine design?
What is the main purpose of using recombinant DNA techniques in vaccine design?
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Why are small peptide vaccines attached to carrier proteins?
Why are small peptide vaccines attached to carrier proteins?
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Which of the following is a common characteristic of subunit vaccines?
Which of the following is a common characteristic of subunit vaccines?
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Study Notes
Recombinant and Synthetic Vaccines III
- Vaccine antibody production requires both B cell and T cell epitopes.
- Subunit protein vaccines, being large proteins, contain both.
- Polysaccharide vaccines present a limitation—they lack T cell epitopes.
- To address this, carrier proteins are utilized.
- This creates conjugate vaccines capable of immunizing infants effectively.
Improving the Effectiveness of Subunit Vaccines
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Strongest immune responses occur with concentrated antigens.
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Pure subunit vaccines generally produce weaker responses than whole pathogens.
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Hepatitis B and human papillomavirus surface antigens uniquely assemble into particles similar to empty virus particles.
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Various methods fix numerous antigenic protein molecules onto particulate carrier surfaces.
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Insoluble aluminum salts act as adjuvants.
- They maintain high immunogen concentration locally.
- This ensures effective presentation of antigens.
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MF59, an oil-in-water emulsion, is a new adjuvant.
- It contains squalene and detergents.
- Amphiphilic immunogens concentrate at the oil/water interface.
- This assists in the creation of effective influenza vaccines.
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Another approach enhances subunit antigens by using the hepatitis B surface antigen's self-assembling property.
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This involves fusing other subunit antigens to the hepatitis B surface antigen.
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Recombinant DNA technique (genetic engineering) is central to this method.
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Adjuvants that interact with Toll-like receptors are utilized.
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Synthetic analogs of the natural adjuvant muramyldipeptide (MDP) have been explored.
- MDP is a fragment of bacterial peptidoglycan.
- Modifications (e.g., replacing L-alanine with L-threonine) are made to avoid unwanted side effects.
- This helps achieve potent immune responses.
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Another type of adjuvant—monophosphoryl lipid A and its derivatives—interact with Toll-like receptors.
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These compounds share structural similarities with LPS (specifically its lipid portion, lipid A) but are significantly less toxic.
Use of Live, Attenuated Vectors
- Live, attenuated vaccines introduce subunit antigens into live, attenuated viruses or bacteria.
- This approach often confers stronger, longer-lasting immunity than killed vaccines.
- Live vaccines are typically delivered in lower doses compared to killed vaccines; they can multiply within the host.
Fragments of Antigen Subunit Used as Synthetic Peptide Vaccines
- Subunit vaccines utilize one or a few macromolecular components of the pathogen.
- Only the most critical parts (epitopes) of the pathogen are needed for proper binding.
- This approach permits the targeting of desired epitopes and allows greater control of the immune response.
- Peptides are usually attached to macromolecular carrier proteins before administration.
Peptide Vaccine Advantages
- Peptides can be chemically synthesized.
- Less purification is required compared to recombinant subunit-based vaccines.
- Purification is often difficult and expensive.
- This makes peptide vaccines more cost-effective, pure, and stable.
- Peptides play a role in generating cellular immunity by selecting T cell clones.
DNA Vaccines
- Injected DNA into mice resulted in foreign gene expression.
- This suggests potential gene expression in animals.
- Plasmid DNA containing pathogen antigen genes creates immunity.
- DNA vaccines are easily modified, facilitating the production of new and tailored vaccines.
- Steps needed for conventional protein vaccines, like purification, are less critical with DNA vaccines.
- The antigen gene in DNA vaccines can be expressed within antigen-presenting cells (APCs).
- This means immune response is strongly directed towards cytotoxic CD8 T cells.
DNA Vaccine Mechanisms of Action
- Foreign DNA from pathogens is transcribed, and translated into protein by cells, resulting in presentation of these foreign antigens.
- Cells (especially APCs and T cells) then interact, leading to an immune response.
DNA Vaccine Success in Humans
- Significant research focuses on creating effective DNA vaccines.
- Initial successes were observed, but DNA vaccines are often not potent enough for use in humans.
- Increasing potency is a major research focus.
- By enhancing the introduction method.
- Combining initial DNA vaccine delivery with subsequent booster shots.
- Despite this, recent clinical trials using antimalarial DNA vaccines showed no effect even with boosters.
DNA Vaccine Dosage Considerations
- Initial research in mice utilized much higher doses than appropriate for humans.
- Larger human doses are impractical to administer and produce.
- Manufacturing large amounts is expensive.
- Current human trial usage is significantly lower than those used in initial mouse tests.
- Research focuses on determining optimal doses.
Novel Approaches for DNA Vaccines
- Additional strategies are being explored to improve DNA vaccine effectiveness and safety.
- One possible consideration is the integration of foreign plasmid DNA into human chromosomes.
- While this risk is theoretically low, experiments have shown that successful vaccines will be administered to massive populations, even billions, in which scenario, any potential adverse events must be viewed seriously.
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