News shared by the University of Queensland (UQ) in December 2023 explains how a paper in Molecular Therapy Nucleic Acids presents positive results from a study investigating the stability, efficacy, and immunogenicity of a DNA vaccine delivered to the skin through HD-MAP technology. The vaccine was developed to protect people from the “potentially deadly mosquito borne Zika virus”. This technology, developed by UQ and commercialised by Vaxxas, has previously been financially recognised by CEPI and Wellcome.
Zika
The researchers describe Zika virus (ZIKV) as a “re-emerging flavivirus” that is most frequently transmitted by blood meals of a mosquito. However, sexual and vertical transmission have been “well-documented”. First identified as a cause of human infections in the 1950s, it has caused “sporadic outbreaks”; an example of this was the 2015-2016 outbreak, during which “millions” of people in the Americas were believed or confirmed to be infected.
Despite a decline in global incidence of ZIKV researchers emphasise how “important” it is to “continue ZIKV vaccine development” for emergency use in the “likely event” of a future outbreak. The ZIKV genome encodes three structural proteins that are important for cell entry including premembrane (prM) and envelope (E); most vaccine development efforts have focused on targeting prM and E. Unfortunately, antibodies against the virion surface E protein reportedly have the potential to enhance infection of dengue virus, and vice versa, in countries where the viruses co-circulate.
DNA vaccines
“DNA vaccines are inexpensive, easy to construct, stable at room temperature, and have minimum side effects, which simplifies handling and distribution, suggesting the potential for equitable global distribution of this type of vaccine.”
The study suggests that DNA vaccines that elicited protective neutralising antibodies to ZIKV in mice and rhesus macaques were developed. The team developed a proprietary DNA vaccine (pVAX-tpaNS1) that encodes codon-optimised NS1 protein from the Brazilian strain of ZIKV with a tissue plasminogen activator signal sequence to facilitate effective NS1 secretion. However, the “potential” of the DNA vaccines is “still not fully realised” because of “poor delivery and antigen expression” as well as the “lack of a localised inflammatory response”.
DNA vaccines derive “significant” benefits from delivery into the dermal layers of the skin. Therefore, the high-density microarray patch (HD-MAP) vaccine delivery technology is once again tested, in this case to see if pVAX-tpaNS1 could elicit more potent NS1-specific immunity in vivo and protection against ZIKV in comparison with ‘traditional’ needle and syringe vaccination.
A better method
Dr Danushka Wijesundara, UQ alum and Vaxxas researcher, commented that the virus presents a risk to many people across the globe, but the latest research shows a potential improvement to disease control.
“We can change the way we combat Zika virus with the HD-MAP patch because it is an effective, pain-free, simple to apply, and easy to store vaccination method.”
Dr Wijesundara suggests that in the trial “the vaccine provided rapid protection against live Zika virus”.
“The vaccine patch evoked T-cell responses that were about 270% higher than from a needle or syringe vaccine delivery.”
The University of Adelaide’s Associate Professor Branka Grubor-Bauk states that, while there is no licensed vaccine, the virus is known to be active in at least 89 countries and territories.
“This vaccine is unique because it targets a protein inside, rather than outside of the virus meaning it won’t enhance the symptoms of closely related viruses.”
Dr David Muller of UQ hopes that the team’s research will have applications beyond a potential Zika vaccine.
“Because the protein we’re targeting plays a central role in replication in a virus family known as flaviviruses, there’s the potential to apply our approach to target other flaviviruses such as dengue or Japanese encephalitis.”
Furthermore, the technology could deliver a vaccine “mixture” to target the “whole family” and provide “greater protection”. Finally, Dr Muller reflects that a “major benefit” of the HD-MAP platform is the “vaccine stability at elevated temperatures”.
“We found the patch retained vaccine potency when stored at 40 degrees Celsius for up to four weeks…This increases the reach of vaccines in low- and middle-income countries where refrigeration is challenging.”
We look forward to hearing more from Vaxxas on their unique delivery approach at the Congress in Washington next year. You can join us by getting your tickets here or subscribe for more updates on vaccine technology.
