A misunderstanding of the results of a recently presented phase I HIV vaccine study has prompted an outbreak of misinformation on social media. Several erroneous claims are being made, including:
- That it was an mRNA vaccine - it was a specially engineered protein plus an adjuvant.
- That it induced antibody responses against HIV in 97% of the trial participants - antibody responses were not measured in the study.
- That the vaccine will be tested for efficacy - it won't be, it's only a first "priming" vaccine that will need to be followed by booster vaccines that haven't been designed yet.
The study results were presented by William Schief at the recent R4P virtual conference and the primary sponsors of the work, the Scripps Research Institute and IAVI, both issued a press release back on February 3rd. The results do potentially represent good news, but unfortunately they don't mean that an efficacious HIV vaccine is imminent (as many viral social media posts have suggested).
In reality, the research represents a highly technical effort to bolster the number of B cells that might eventually - with further encouragement by additional vaccines - have the capacity to produce antibodies capable of effectively inhibiting HIV (broadly neutralizing antibodies or bNAbs for short). Inducing bNAbs is the Holy Grail of HIV vaccine research. The approach under study is referred to as a germline targeting strategy (germline refers to B cell genes that may represent a starting point for bNAb generation).
Over the past decade or so, new technologies have allowed scientists to discover that some people with HIV slowly develop bNAbs against the virus. These bNAbs are typically present at too low a level in the body to benefit the individual, but it's possible for researchers to fish out the B cells that produce them. The genetic code within the B cell responsible for producing the bNAb can then be used as a template to manufacture large amounts of the antibody. This has allowed the initiation of clinical trials in which bNAbs are infused or injected subcutaneously both as potential HIV treatments and preventive interventions.
The approach being taken by Schief and colleagues uses knowledge about how B cells shuffle their genetic code to produce progressively superior antibodies - a process called somatic hypermutation - to figure out how the process of bNAb production might be stimulated with a vaccine.
The phase I trial that's caused the online hooplah was the first attempt to boost the number of a certain type of B cell in humans that could represent a starting point on the pathway toward bNAb production. Metaphorically, it's like trying to create a pool of B cell trainees that can then be further educated until they hopefully become capable of making bNAbs against HIV. The researchers used a specially designed protein named eOD-GT8 60mer administered with an adjuvant (AS01B) to immunize trial participants.
The trial was a success in terms of reaching its goal. Almost all (35 of 36 or 97%) of the vaccine recipients displayed the desired type of B cell after immunization, whereas only five had detectable levels of the B cell prior to immunization. In some of the incorrect social media posts, this result has been misrepresented as showing that 97% of recipients showed antibody responses against HIV (antibody responses weren't measured).
The next steps for this research will involve designing additional vaccines (which Schief refers to as "shepherding" and "polishing" vaccines) that aim to complete the education of the trainee B cells and thus prompt bNAb production. This is likely to be a lengthy process, and success isn't guaranteed.
The mistaken claims on social media that the vaccine involved mRNA likely arose because the researchers plan to collaborate with Moderna to deliver the protein used in the study (and potentially other proteins) via mRNA in the future. Hopefully the use of mRNA can accelerate the evaluation of candidate proteins that are designed to coax B cells further down the pathway toward making bNAbs.
Unfortunately it can't be assumed that simply applying mRNA technology to HIV vaccines would lead to similar efficacy to that seen with COVID-19 vaccines. HIV has evolved to be highly resistant to antibody responses, which is not the case for SARS-CoV-2. The reason bNAbs against HIV (and the B cells that make them) are rare is that the antibodies need to have unusual shapes to penetrate the cloak of sugar molecules that shrouds HIV's outer Envelope protein. But the fact that bNAbs can nevertheless arise gives hope that the work of Schief and colleagues will ultimately pay off.
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