GALVESTON, Texas – Researchers at The University of Texas Medical Branch at Galveston have developed a less expensive way to produce vaccines that cuts the cost of vaccine production and storage by 80 percent without decreasing safety or effectiveness. The findings are currently available in EBioMedicine.
Vaccines are the most effective way to prevent and eradicate infectious diseases. Currently, many vaccines have to be manufactured in cell culture or eggs, which is expensive and carries the risk of contaminations. In addition, most vaccines must be kept refrigerated during the transportation from manufacturers to health care clinics. In tropical and subtropical regions, such cold storage requirements could contribute to more than 80 percent of the vaccine cost.
“The ability to eliminate cell culture or eggs and cold storage will change the process of vaccine development,” said UTMB’s Pei-Yong Shi, professor in the department of biochemistry and molecular biology. “Importantly, this vaccine technology could potentially serve as a universal platform for development of live-attenuated vaccines for many viral pathogens.”
To achieve these goals, the UTMB team engineered a live-attenuated Zika vaccine in the DNA form. Once the DNA is delivered into our body, it launches the vaccine in our cells, leading to antibody production and other protective immunity. With this production method, there is no need to manufacture the vaccine in cell culture or eggs at factories. Because DNA molecules are shelf stable, the vaccine will not expire at warm temperatures and could be stockpiled at room temperature for years.
Using UTMB’s Zika vaccine as a model, the research group showed that the DNA platform worked very efficiently in mice. After a single low dose, the DNA vaccine protected mice from Zika virus infection, mother-to-fetus transmission during pregnancy and male reproductive tract infection and damage.
“This is the first study to demonstrate that, after a single low dose, a DNA vaccine could induce saturated protective immunity,” Shi said. “We will continue testing this promising Zika vaccine platform and then apply the platform to other viruses.”
Other authors include UTMB’s Jing Zou, Xuping Xie, Huanle Luo, Chao Shan, Antonio Muruato, Scott Weaver and Tian Wang.
Pinch_roll on October 7th, 2018 at 03:38 UTC »
I work in the field of DNA vaccines, so I thought I'd add some context. DNA vaccines have been around for many decades. Unfortunately, injecting plasmids into mice often produces amazing results like these, but scaling up into larger animals and finally humans is always problematic. Plasmid injections are simply not efficient enough to transfect sufficient numbers of cells in a human to generate meaningful immune responses. That's a good thing most of the time! Cells are designed to not simply let free floating DNA pass through the cell membrane, or else we would be susceptible to all kinds of diseases. Unfortunately, this is a major barrier to actually delivering a meaningful dose. In a small animal like a mouse you can perform a small plasmid injection into the leg and pretty much transfect the whole muscle. Now you have a (relatively) giant factory of muscle cells producing antigen. In a human, a standard (1 mL) injection of plasmid DNA transfects a miniscule number of cells and now you have a comparatively tiny factory of antigen production that struggles to elicit any appreciable immune response.
Nowadays, delivering nucleic acid vaccines into humans requires a delivery system. In humans, that usually means electroporation, which is the gold standard for in vivo DNA delivery because it also seems to promote a strong cellular immune response, which is a unique advantage compared to viral vectors. Also, RNA delivery is becoming a hot topic as well due to some other advantages that I won't get into, but usually requires a special formulation to stabilize and deliver the drug because RNA tends to break down rapidly (whereas plasmid DNA is incredibly shelf stable, as the article points out).
TL;DR: DNA vaccines are not new, and they look miraculous in mice but have crashed and burned in a ton of clinical trials because they need a special delivery system in humans. The title is very misleading because the platform isn't new, even if the specific construct used in this study is.
Ectar93 on October 7th, 2018 at 02:17 UTC »
Now watch the patent owners make it so expensive to use that it's just cheap enough for most institutions to use over the current options.
mvea on October 7th, 2018 at 01:16 UTC »
The title of the post is a copy and paste from the title, first and fourth paragraphs of the linked academic press release here :
Journal Reference:
Jing Zou, Xuping Xie, Huanle Luo, Chao Shan, Antonio E. Muruato, Scott C. Weaver, Tian Wang, Pei-Yong Shi,
A single-dose plasmid-launched live-attenuated Zika vaccine induces protective immunity,
EBioMedicine, 2018, ISSN 2352-3964,
Doi: https://doi.org/10.1016/j.ebiom.2018.08.056
Link: http://www.sciencedirect.com/science/article/pii/S2352396418303499
Abstract:
Background
Vaccines are the most effective means to fight and eradicate infectious diseases. Live-attenuated vaccines (LAV) usually have the advantages of single dose, rapid onset of immunity, and durable protection. DNA vaccines have the advantages of chemical stability, ease of production, and no cold chain requirement. The ability to combine the strengths of LAV and DNA vaccines may transform future vaccine development by eliminating cold chain and cell culture with the potential for adventitious agents.
Methods
A DNA-launched LAV was developed for ZIKV virus (ZIKV), a pathogen that recently caused a global public health emergency. The cDNA copy of a ZIKV LAV genome was engineered into a DNA plasmid. The DNA-LAV plasmid was delivered into mice using a clinically proven device TriGrid™ to launch the replication of LAV.
Findings
A single-dose immunization as low as 0.5 μg of DNA-LAV plasmid conferred 100% seroconversion in A129 mice. All seroconverted mice developed sterilizing immunity, as indicated by no detectable infectious viruses and no increase of neutralizing antibody titers after ZIKV challenge. The immunization also elicited robust T cell responses. In pregnant mice, the DNA-LAV vaccination fully protected against ZIKV-induced disease and maternal-to-fetal transmission. High levels of neutralizing activities were detected in fetal serum, indicating maternal-to-fetal humoral transfer. In male mice, a single-dose vaccination completely prevented testis infection, injury, and oligospermia.
Interpretation
The remarkable simplicity and potency of ZIKV DNA-LAV warrant further development of this vaccine candidate. The DNA-LAV approach may serve as a universal vaccine platform for other plus-sense RNA viruses.