“More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016”
This stark opening statement in a recent paper published by Barouch et al in The Lancet highlights how the HIV global pandemic is still afoot, and many individuals worldwide are still at high risk of infection. Lack of access to antiretroviral treatment and to prophylactic care still present a hurdle to eradicating HIV-1. Therefore, an efficacious and durable vaccine against HIV-1 would release burden on healthcare systems and governments, and furthermore prevent transmission among those to whom current treatments are unavailable.
However, the task is not a simple one. HIV-1 is an incredibly complex virus, made apparent by its rapid rates of mutation upon infection. This makes it near-impossible for the human immune system to mount a strong enough defense, before the virus changes into something that can no longer be recognised.
What is the vaccine made of?
The vaccine outlined in this paper is an viral vectored vaccine, containing the parts of HIV that are most frequently recognised by the human immune system. Viral vectored vaccines are, simply, viruses that have been altered, chopped up, and modified so that they are no longer dangerous to humans, but can still be used to express parts of other pathogens, such as HIV, to initiate an immunological response. This vaccine is made from adenovirus (the common cold virus) as the vector, expressing a mosaic peptide of Env, Gag, and Pol peptides from multiple different strains of HIV-1. A booster vaccine, created from MVA (modified Vaccinia Ankara), another virus also containing the mosaic HIV peptide, was also given to some volunteers. Some participants also received a dose of gp140, another HIV peptide, to see if this increased immune response.
Why use a vaccine made from different types of HIV?
Using ‘mosaic’ peptides, created from different strains of HIV-1, decreases the likelihood that an infecting virus will mutate into something that the immune system can’t recognise. This would potentially allow the immune system to generate a strong enough response to clear the virus, before it can no longer be detected. It also raises the possibility of protection against multiple types of HIV-1.
The vaccine trial
The aim of this trial was not to protect volunteers from HIV, but instead to test the tolerance (how well people felt after the vaccine) and immunogenicity (what sort of immune response could be measured after the vaccination). The vaccine induced strong antibody responses, which were increased with the booster vaccine later during the study, and in individuals who also received the gp140 booster. The vaccine also stimulated robust T-cell responses against the HIV-1 peptides in the vaccine, measured through production of interferon-gamma, a soluble, toxic protein that T-cells produce to kill infected cells. The T-cells induced by this vaccine consisted of the two main types of T-cells, CD4 and CD8, and were able to react against all the HIV-1 peptides in the vaccine. Ultimately, the most effective regimen was first vaccinating with the adenovirus-vectored HIV vaccine, followed by the MVA-vectored vaccine and gp140 boost.
Given the success of the vaccine in this primary study, alongside matching pre-clinical trials, this vaccine is now being tested in a phase II efficacy trial. Although still a long way from a licensed, efficacious vaccine against HIV-1, at this early stage there is promise that this vaccine will contribute towards our knowledge of how to tackle the ongoing worldwide HIV-1 pandemic.
The paper: Barouch et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). 2018. The Lancet.
words in pink can be found in the glossary