HIV vaccine development: past, present and future Flashcards
What are HIV vaccine challenges?
Antigenic diversity and hypervariability of the virus.
Integration of the viral genome into host cell chromosomes.
Persistence of the virus in a latent state in resting memory T-cells.
Rapid emergence of viral escape mutants in the host.
Transmission by mucosal routes.
What are the limitations of humanized mice as a model for HIV?
The induction of immune responses against HIV is not optimal.
What are the disadvantages of using HIV-2/SIV as a model for HIV-1 in monkeys?
There is a genetic difference, especially in the envelope so it’s not possible to evaluate antibody-based vaccine protection (directed against the Env protein).
Solution: using HIV-2/HIV-1 chimeric viruses that carry HIV-1 Env protein (SHIV).
Why are the classical vaccination approaches against HIV not good?
Live attenuated viruses are not safe because they integrate into the genome and can induce disease. Whole inactivated viruses give no protection against infection.
Why are we researching protein subunit vaccines against HIV?
By using the HIV envelope protein we get protection against HIV-1 and SHIV in monkeys. However, there is only protection against homologous viruses and lab adapted viruses (not primary HIV-1).
What are the challenges for the induction of broadly virus-neutralizing antibodies?
the trimeric configuration of Env, complex receptor interaction mechanism, glycoprotein shield, variable regions in the envelope, and viral diversity.
How do vaccines inducing cytotoxic responses work?
Boost strategies give greatly increased immune responses but no protection against infection.
Mosaic vaccines cover a range of mutations and boost regimens with different viral vectors.
