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mRNA HIV Vaccine Hits Major Hurdle In Clinical Trials
Moderna has hit a roadblock developing an mRNA vaccine for HIV.
“HIV mRNA Vaccine has failed Phase I trials – it has ‘puzzling skin side effects’ in up to 20% of vaccine recipients‚ according to a new article in ‘Science’. But they are pushing forward anyways‚” William Makis MD wrote.
“Moderna’s HIV mRNA Vaccine just failed Phase I trials‚ according to a new article published in Science on March 1‚ 2024. Up to 20% of the HIV mRNA Vaccine victims developed skin rashes‚ welts or other skin irritations‚” he added.
NEW ARTICLE: HIV mRNA Vaccine has failed Phase I trials – it has "puzzling skin side effects" in up to 20% of vaccine recipients‚ according to a new article in "Science". But they are pushing forward anyways.
Moderna's HIV mRNA Vaccine just failed Phase I trials‚ according to a… pic.twitter.com/bCPsEzpfVg
— William Makis MD (@MakisMD) March 18‚ 2024
“One of the most promising attempts to reinvigorate the stalled quest for an HIV vaccine has hit a snag that might seem minor but has major consequences: delaying the larger trials needed to show whether the concept works. In small safety and immune tests of the innovative vaccine strategy‚ which relies on a series of messenger RNA (mRNA) shots‚ an unusually high percentage of recipients developed rashes‚ welts‚ or other skin irritations‚” Science wrote earlier this month.
From Science:
“We are taking this very seriously‚” says Carl Dieffenbach‚ who heads the Division of AIDS at the National Institute of Allergy and Infectious Diseases‚ which funded a recent phase 1 trial of the vaccine. Researchers want to understand the cause of the skin problems and how to minimize them before expanding tests of the vaccines‚ which are made by Moderna. “We would be moving more quickly if this finding had not been observed‚” says Mark Feinberg‚ who heads IAVI‚ a nonprofit that is the vaccine’s major sponsor.
The complex vaccine strategy involves injections of different mRNAs‚ encoding various pieces of HIV’s surface protein or the entire molecule‚ over the course of several months. The goal is to gradually guide the immune system’s B cells to produce so-called broadly neutralizing antibodies‚ or bnAbs‚ capable of stopping many different variants of the AIDS virus. People living with HIV on rare occasions eventually produce bnAbs‚ but no vaccine has ever done so—which has become the “holy grail” for the field‚ says Linda-Gail Bekker‚ an AIDS vaccine researcher in South Africa who runs the Desmond Tutu HIV Centre at the University of Cape Town.
Different versions of this HIV vaccine have already gone through three phase 1 trials‚ but they totaled fewer than 200 participants. The recipients responded with impressive antibodies that were moving toward bnAbs‚ fueling hopes for the vaccines. But skin problems—including urticaria (hives)‚ pruritus (itching)‚ and dermatographism (welts after scratching)—occurred at a noticeably high level in all of the studies‚ affecting 11 out 60 people in one of them.
These HIV vaccines deliver a relatively high dose of mRNA‚ which Moderna scientists and others think could explain the skin issues. The company’s original COVID-19 mRNA vaccine used the same dose and has also been linked to skin problems‚ although at much lower frequencies‚ of 1% to 3%. (The Pfizer-BioNTech collaboration’s COVID-19 vaccine‚ also based on mRNA but given at a 70% lower dose‚ triggers skin problems‚ too‚ but one Swiss study suggests they occur 20 times less frequently than with the Moderna product.) Potentially more worrisome‚ however‚ would be if the problem is tied to a cumulative effect from multiple mRNA shots or the genetic background of the recipients‚ or if the HIV sequence itself were responsible for the welts and hives.
“NIAID now plans to repeat the phase 1 trials of some of these Moderna/IAVI HIV vaccines with a lower dose‚” Science noted.
Partners for mRNA HIV vaccine trials include:
International AIDS Vaccine Initiative (IAVI)
Moderna
HIV Vaccine Trials Network (HVTN)
National Institutes of Health (NIH)
Bill &; Melinda Gates Foundation
“IAVI and partners have observed that skin events occurred in 7%-18% of the volunteers who received the investigational products across IAVI G002 (NCT05001371)‚ IAVI G003 (NCT05414786)‚ and HVTN 302 (NCT05217641). It’s important to note that none of the studies had control arms‚ which would have helped clarify the actual frequency of skin events that are associated with the specific vaccine candidates studied‚” IAVI wrote in a statement on the mRNA HIV vaccine candidate.
From IAVI:
The affected volunteers in the trials had skin events that were described as hives‚ itchiness‚ or hives caused by scratching. Most of these events were mild or moderate‚ and managed with simple allergy medications. There were no serious adverse events reported. Participants who experienced skin events were provided all medical care necessary and were monitored closely.
IAVI and partners are actively working to investigate the potential causes of these skin events. We have brought in an interdisciplinary team of external experts‚ including allergists and immunologists‚ to further assess the skin events. In the interest of transparency and clarity‚ IAVI and partners have presented preliminary data on immune responses and safety at scientific conferences and look forward to continuing our discussion of these results. Communicating details about the safety and immunogenicity of our vaccine candidates in a clear‚ timely‚ and transparent way is a top priority for IAVI and our partners.
The skin events observed in the trials were not observed in an earlier trial that evaluated a recombinant protein version of one of the immunogens used in IAVI G002.
Mark Feinberg‚ M.D.‚ Ph.D.‚ IAVI’s president and CEO‚ said‚ “IAVI is encouraged by the very favorable immunogenicity results seen in IAVI G002 and related trials‚ which will be published in forthcoming papers. We look forward to continuing our pursuit of proof-of-concept for the elicitation of broadly neutralizing antibodies against HIV via the defined sequential germline-targeting immunization strategy‚ while working to better understand this safety signal and identify approaches to mitigate it. We will continue safety and immunogenicity studies of scientifically promising immunogens that we hope will be part of a much-needed HIV vaccine.”