Development strategies and immunization objectives
Successful experiments on monkeys with SIV (simian immunodeficiency virus) and SHIV (recombinant virus) have proved that developing an HIV vaccine is theoretically possible. To date, both prophylactic and therapeutic vaccines are being developed.
Researchers face two main objectives, which can be pursued either separately or in combination:
- Induction of effective neutralizing antibody production.
- Activation of cellular immunity (primarily cytotoxic CD8+ T lymphocytes) capable of eliminating the virus or at least halting the progression of the infection.
Conserved epitopes of the virus serve as targets. These include the coreceptor binding site and invariable regions of the gp41 protein. The main difficulty lies in the fact that these epitopes are poorly accessible to the induced antibodies.
Technologies and composition of candidate vaccines
Vaccine development is overseen by the Global HIV/AIDS Vaccine Enterprise (Global HIV/AIDS vaccine enterprise). Most modern candidate vaccines are based on DNA vectors (often as plasmids), recombinant proteins, and combinations thereof.
Vaccine compositions most frequently replicate epitopes of the Gag and Pol proteins. To stimulate cellular immunity, dendritic cells pre-loaded with viral antigens are used. To activate the innate immune system, novel adjuvants and components targeting TLRs (Toll-like receptors) are incorporated into the vaccines.
Note: Live attenuated vaccines are prohibited for use in humans due to high risks, although they showed good efficacy in primate experiments.
Preclinical trials and administration regimen
At the preclinical research stage, scientists select optimal animal models and develop methods to assess various branches of the immune response.
The prime-boost regimen—a two-step immunization—is considered the most effective administration strategy. Different types of preparations can be used at various stages. For example, a DNA vaccine is used for priming (first injection), and a recombinant protein is used for boosting (repeated injection).
Russian developments
Several promising candidate vaccines have been developed in Russia.
VICHREPOL Developed by the Institute of Immunology of the Federal Medical-Biological Agency (FMBA) in collaboration with the Ivanovsky Institute of Virology (RAMS). It is based on a chimeric recombinant protein rec. This protein consists of the full-length sequence of the internal protein p24 (gene Gag) and an immunoreactive fragment of the gp41 protein (gene Env). The presence of the p24 epitope stimulates the T-cell response, while the vaccine as a whole aims to induce neutralizing antibodies. The conjugated polymeric immunomodulator polyoxidonium is used as an adjuvant. In preclinical tests, the agent demonstrated a potent humoral response; clinical trials started in 2006.
Vector Center Products
- CombiHIVvac is an injectable virus-like particle vaccine. It contains the pcDNA-TCI plasmid inside (encoding a number of HIV epitopes), and the TBI protein on the surface (containing 4 T-epitopes and 5 B-epitopes from various viral proteins).
- SAL-HIV are suppositories designed to induce mucosal immunity. They consist of attenuated Salmonella enteritidis bacteria containing the pcDNA-TCI plasmid inside.
Briefly: answers to topical questions
What specific animal models are used during the preclinical trial phase of HIV vaccines?
During the preclinical trial phase of HIV vaccines, monkeys are used as animal models. Particular attention during the research is paid to developing optimal models for testing various components of the immune system:
- Monkeys are used for vaccination against SIV (simian immunodeficiency virus) and SHIV (recombinant simian/human immunodeficiency virus).
Successful immunization of these animals proves the theoretical feasibility of developing such a preparation. Furthermore, it was specifically in monkeys that live attenuated vaccines demonstrated high efficacy, though they are currently prohibited for administration to humans for safety reasons.
Class and exam questions
Why are HIV vaccines referred to as "candidate" vaccines?
Due to the extremely high complexity of development, no preparation has yet proven complete clinical efficacy, which is why all developing vaccines retain candidate status.
Which HIV vaccine administration regimen is considered optimal?
The prime-boost regimen is optimal—a two-dose administration of preparations, where vaccines of different types (e.g., a DNA vaccine and a recombinant protein) are often used for priming and boosting.
Are live HIV vaccines used?
No. Despite the efficacy demonstrated in monkeys, live attenuated HIV vaccines are prohibited in humans for safety reasons.
What else to study on this topic
- Structural features of HIV Gag, Pol, and Env proteins
- Structure and functions of HIV coreceptors and the gp41 protein
- Mechanism of action of DNA vector vaccines
- The role of Toll-like receptors (TLRs) in immune stimulation
- Application of dendritic cells in immunology
- Differences between prophylactic and therapeutic vaccines
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Other topics in the section "Immunity in defense and damage of the organism. Pathology of immunity"
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