HIV vaccine development

In 1984, after it was confirmed that HIV caused AIDS, the United States Health and Human Services Secretary Margaret Heckler declared that a vaccine would be available within two years.

[2] However, priming the adaptive immune system to recognize the viral envelope proteins did not prevent HIV acquisition.

Furthermore, the functionally important epitopes of the gp120 protein are masked by glycosylation, trimerisation and receptor-induced conformational changes making it difficult to block with neutralizing antibodies.

[6] It had been observed that a few, but not all, HIV-infected individuals naturally produce broadly neutralizing antibodies (BNAbs) which keep the virus suppressed, and these people remain asymptomatic for decades.

Only the functional portions of Env remain constant, but these are generally hidden from the immune system by the molecule's structure.

An NCI research team led by Dr. Sriram Subramaniam used cryo-electron microscopy to examine the Env structure.

Researchers hypothesized that vaccines designed to maintain activated effector memory T cells might impair viral replication at its earliest stage.

Target cell proliferation and oligoclonal expansion are induced by the virus, which suggests repressed immunity seen in mice thus referred to as paraneoplastic syndrome.

Mammalian derived envelope preparations have been better inducers of neutralizing antibody than candidates produced in yeast and bacteria.

Although the vaccination process involved many repeated "booster" injections, it was challenging to induce and maintain the high anti-gp120 antibody titers necessary to have any hope of neutralizing an HIV exposure.

The canarypox vector is the first candidate HIV vaccine that has induced cross-clade functional CTL responses.

The study determined the extent to which Ugandan volunteers have CTL that are active against the subtypes of HIV prevalent in Uganda, A and D. In 2015, a Phase I trial called HVTN 100 in South Africa tested the combination of a canarypox vector ALVAC and a gp120 protein adapted for the subtype C HIV common in sub-Saharan Africa, with the MF59 adjuvant.

[18] Other strategies that have progressed to phase I trials in uninfected persons include peptides, lipopeptides, DNA, an attenuated Salmonella vector, p24, etc.

[25][26] On January 17, 2022 IAVI and Moderna launched a phase I trial of a HIV vaccine with mRNA technology.

[27] On March 14, 2022 the National Institutes of Health reported that it had launched a "clinical trial of three mRNA HIV vaccines".

Here are the different classification of methods: Inhibiting the life functions of infected cells: There have been reports that HIV patients coinfected with GB virus C (GBV-C), also called hepatitis G virus, can survive longer than those without GBV-C, but the patients may be different in other ways.

[51] Live attenuated vaccines are highly successful against polio, rotavirus and measles, but have not been tested against HIV in humans.