Immune-Based Modulators

Therapeutic vaccines

There are two types of immune responses, referred to as innate and adaptive immunity. The innate response is the first line of defense against pathogens, and is considered to be more general and non-specific. The second line of defense, the adaptive immune response, recognizes specific pathogen fragments, called antigens. CD4 T cells, CD8 T cells and B cells are all part of the adaptive immune system. T cells and B cells are activated when presented with antigens, including by HIV antigens. HIV therapeutic vaccines expose an HIV-positive individual to HIV antigens that are designed to elicit a more effective adaptive immune response to the virus.

There are four strategies used to deliver non-infectious HIV antigens into the patient:

• DNA and RNA vaccines: These genetic vaccines use DNA plasmids or mRNA that code for the antigen. They are then taken up by the patient’s cells, which then start to produce that specific antigen. 

• Viral vector vaccines: Genes encoding HIV antigens such as HIV envelope protein are inserted into a modified, non-pathogenic virus (for example, canarypox).

• Protein or peptide vaccines: HIV proteins or protein fragments are delivered in this class of vaccine.

• Dendritic cell vaccines: In this case, antigen-presenting dendritic cells are isolated from a patient and mixed with HIV antigens. These cells are then injected back into the patient. 

What happens to antigens after they are introduced to an individual? Antigens are internalized and processed by immune system sentinels called antigen-presenting cells (specifically, dendritic cells and macrophages). These antigen fragments are then presented to helper T cells. Specific helper T cells can become activated after being presented with these antigens, causing them to activate and proliferate into clones. This army of helper T cells can release different signals that activate B cells to start producing antibodies. At the same time, cytotoxic T cells, which also recognize the same target antigen, are activated.

When cytotoxic T cells interact with infected cells that are displaying the specific target antigen on their surface (on proteins known as MHC1 receptors), the T cells produce granzymes and perforin which cause the infected cell to break down. 

Broadly Neutralizing Antibodies - Passive Immunization

Some bnAbs have been isolated from the B cells of HIV-positive individuals and sequenced. These bnAbs can then be manufactured and administered by subcutaneous injection or infusion to other infected individuals. The bnAbs can then recognize infected cells and target them for destruction by natural killer cells.