Skin vaccination with microneedle patch, influenza fusion protein improves efficacy of flu vaccines

July 19, 2017 by Latina Emerson
Credit: Georgia State University

A boosting skin vaccination with a biodegradable microneedle patch and protein constructed from sequences of influenza virus subtypes could improve the effectiveness of conventional influenza vaccines, according to a study led by Georgia State University.

To increase the protection offered by standard influenza vaccines, Dr. Baozhong Wang's group made a fusion protein (4M2e-tFliC) with four different sequences of M2e from four different influenza subtypes. M2e is a peptide, a compound of two or more amino acids linked in a chain, found among all influenza strains. The fusion protein also contains flagellin (FliC), a peptide found in nearly all bacteria with flagella (lash-like appendages) that acts as a strong catalyst when administered together with other antigens, or foreign substances that induce an immune response in the body.

The researchers condensed the protein into the microneedle through a collaboration with Dr. Mark R. Prausnitz of the Georgia Institute of Technology. The microneedle patch is generated from a biocompatible polymer, and the tiny needles arrayed on the patch dissolve and release vaccine into the skin rapidly.

The study found mice receiving a conventional inactivated vaccine, a vaccine consisting of pathogens grown in culture and then killed, followed by a skin-applied dissolving 4M2e-tFliC microneedle patch boost could better maintain the humoral immunity antibody response against infection compared to when they received the conventional vaccine alone. The findings, published in the Journal of Controlled Release, offer a new perspective for universal influenza vaccines.

"Our study demonstrates that M2e-based vaccines greatly improve immune responses and strengthen protective functions against ," said Wang, associate professor in the Institute for Biomedical Sciences at Georgia State. "We found that a skin-applied 4M2e-tFliC microneedle patch boosted immunization to seasonal vaccine recipients and may be a rapid approach to increasing the protective efficacy of seasonal vaccines in response to influenza virus challenges. Thus, the M2e antigen is a promising candidate for the development of universal influenza vaccines."

Influenza virus is one of the most serious respiratory pathogens affecting humans and causes about five million illnesses and 250,000 to 500,000 deaths each year worldwide. It's estimated that a sudden emergence of an could kill about 60 million people globally.

Vaccination is an effective method to prevent influenza virus infection, but circulating viruses can rapidly undergo antigenic changes, or small changes in the genes of influenza viruses that happen over time as the virus replicates, that can reduce or eliminate the efficacy of seasonal flu vaccines. To combat an influenza pandemic caused by antigenic drift, a fast, cost-efficient vaccination method is required to provide broader cross-protection against seasonal and pandemic influenza virus infection and promote long-term immunity.

The biodegradable microneedle patch, which is designed to deliver vaccines into the epidermis and dermis of the skin, is a novel technology for vaccine delivery and could improve the 's ability to provoke an immune response in the body. The skin is a potent site for vaccination because it has an abundance of blood vessels and lymphatic vessels, as well as many different immune cell types. Also, many cells in skin express TLR5, a receptor for FliC that activates the innate immune system. Combining the skin delivery of the M2e antigen with tFliC as a catalyst creates a strong synergy.

In this study, mice were immunized with inactivated influenza vaccines, and four weeks later they were given one of the following boosting immunizations: intramuscular injection of 4M2e-tFliC fusion protein, microneedle patch skin vaccination of 4M2e-tFliC or a placebo microneedle patch without the antigen.

The researchers tested whether a 4M2e-tFliC boosting immunization could affect the immune responses induced by inactivated . The mice were challenged with H1N1 and H3N2 influenza viruses and monitored daily for body weight changes and survival over 14 days. The levels of influenza virus titers in the lungs of animals whose bodies had built up antibodies against were measured, and samples of blood, lungs, spleens and bone marrow were collected and processed.

Mice that received the patch boost showed significantly enhanced survival and cellular immune responses. The results also indicated skin vaccination with 4M2e-tFliC aided a long-term antibody-mediated immunity.

Explore further: Microneedle patches for flu vaccination prove successful in first human clinical trial

More information: Wandi Zhu et al. A boosting skin vaccination with dissolving microneedle patch encapsulating M2e vaccine broadens the protective efficacy of conventional influenza vaccines, Journal of Controlled Release (2017). DOI: 10.1016/j.jconrel.2017.06.017

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rderkis
1 / 5 (2) Jul 19, 2017
I don't believe much in conspiracies at all! I really don't.
But what happened to the research talked about here?
https://phys.org/...ola.html
This took one week to develop a vaccine against viruses, bacteria and common parasites with 100% efficiency/cure rate.
This research was done a year ago and would be the greatest medical breakthrough ever discovered.
This research is about a way of producing vaccines not about a particular vaccine. Since it uses RNA it should work on pretty much all animals including humans

Of course it would put most drug companies and health insurance companies out of business. And revolutionize medicare/medicaid.
Yet it seems to have disappeared when somone should be getting the nobel prize for it. ???
rderkis
1 / 5 (1) Jul 20, 2017
No other comments?
I am a skeptic and could not believe the research was real, so I went to MIT's website and it is real!
Doesn't anyone have any comments on why nothing else has been said about it? I am 70 and perhaps I am missing somthing important.
BoatRocker
not rated yet Jul 24, 2017
"...it would put most drug companies and health insurance companies out of business. And revolutionize medicare/medicaid... Yet it seems to have disappeared..."

Yep. I think you pretty much nailed it.
rderkis
not rated yet Jul 24, 2017
Like I said "I don't much believe in conspiracies". If it were a conspiracy of that magnitude that research paper from MIT would never have made it on this site. And if it did somehow make it here, it would have been pulled by now.

They never mentioned it but perhaps each vaccine has to to be custom made for each individual???
Any thoughts on that??
postfuture
not rated yet Jul 24, 2017
I read many articles in NYT, WSJ, etc. about very effective medications that are available in Europe and other countries as over-counter ones but not available for sale in the US. Publications seems did not help. Now I just ask my friends to bring these medications from there.
Let's hope that may be in Europe and other countries they notice this study? Did that news ever appear on Facebook or any other social network? Also although I'm for vaccination as the best available tool for fighting diseases, I personally know someone who is suffering consequences of a serious side effect after a flu shot many years ago.
rderkis
not rated yet Jul 24, 2017
[q Let's hope that may be in Europe and other countries they notice this study? Did that news ever appear on Facebook or any other social network?

I don't know but we are talking about truly groundbreaking medical research. It's kind of like inventing the light bulb. One look and you just knew!
postfuture
not rated yet Jul 24, 2017
i just run a Google search on the last year RNA vaccines research and it seems they are still working on it - www.nature.com/nb...T1.html, www.nature.com/nb...ck=true, www.scientificame...accines/ +++
BoatRocker
not rated yet Jul 24, 2017
rderkis - I try not to do conspiracies, either. That is, I'm (generally) not interested; although, sometimes, not always, it seems the shoe fits, especially with medical breakthroughs and alternative power sources.
But, ET's in UFOs abducting Bigfoot to covert her into a double operative for the Moldavian Intelligence Service to uncover McDonald's secret sauce? Probably not.
And, yes, I just made that up.
Custom made individual, personal vaccines? Now, that would be something.
Still, I think they're talking about assisting immune systems by making flu viruses resemble bacteria*, if I read it right. I'm always happily open to any corrections.

*I think there was a movie about something like this. It didn't end well. At all.
BoatRocker
not rated yet Jul 24, 2017

postfuture - I can relate to the consequences of getting a flu shot as it takes me longer to recover from the immunization than actually getting the flu, and I haven't had the flu or a flu shot for over three decades... So far, so good. Though I have suspected a Typhoid Mary effect I may have on others.

I do (or did) get all the other vaccines: Measles, Mumps (I had Mumps in grade school during the '60's) , Rubella, Small Pox (for international travel), and I think another one or two that I can't remember offhand.

European medication. It's good to have friends. Err... Is that even legal? Some European countries do seem to care more for their citizens then ours (US) does.

Good links guys. One of the main reasons for genetic research, they said way back late last century, was so these kinds of tech/med innovations could be developed.
Custom made individual, personal vaccines... I guess we'll see
rderkis
not rated yet Jul 24, 2017
i just run a Google search on the last year RNA vaccines research and it seems they are still working on it


If I remember right, the Gates foundation gave a terrific amount of money to someone developing a way of creating a super effective vaccine really quickly to fight a possible pandemics. It was just about the time that was released . Suddenly everything about it went dark and I could not find who gates gave the money to. I have wondered if they had any relation to each other or just coincidence.
BoatRocker
not rated yet Jul 25, 2017
Zika?

http://www.cnbc.c...ine.html

"By injecting synthetic mRNA into the body, Moderna says it can direct the body's cells to make proteins, turning cells themselves into drug-producing facilities."
19 May 2017
postfuture
not rated yet Jul 25, 2017

European medication. It's good to have friends. Err... Is that even legal? Some European countries do seem to care more for their citizens then ours (US) does.


It's funny how 'legality' is 1st thing on American mind! It's absolutely legal to bring anything for personal use, it's not legal to sell it in the US. It's not even prescription meds, just over-counter and in many cases plant-based. In EU they even don't like water chlorination any more and started to use ozone, UV (www.waterworld.co...ne.html) Big fuss was over 'chlorinated chickens' imported from the US to EU. They banned it. But we in the US don't mind? But now it's again- Will post-Brexit UK swallow America's "chlorinated chicken" for a trade deal? https://qz.com/10...de-deal/ Read theguardian.com, it's fun!
postfuture
not rated yet Jul 25, 2017
If I remember right, the Gates foundation gave a terrific amount of money to someone developing a way of creating a super effective vaccine really quickly to fight a possible pandemics. It was just about the time that was released . Suddenly everything about it went dark and I could not find who gates gave the money to. I have wondered if they had any relation to each other or just coincidence.


If you are really care about it, why do not contact the Gates foundation directly and ask? They may respond.
rderkis
2 / 5 (1) Jul 25, 2017
If you are really care about it, why do not contact the Gates foundation directly and ask? They may respond.


Every human being should care about it. My guess would be you don't have to contact anybody at least not in the old conventional ways. They probably have a website maintained by their public relations department.
But if they have not said for whatever reason (after all it is their own business), they are not likely to respond to a 70 year old all time underachiever. :-)
boomchakaforever
not rated yet Jul 26, 2017
They used the new technique here.. https://m.phys.org/news/2017-03-rna-nanoparticles-zika.html
But there seems to be done hurdles left to clear... Like a safe effective delivery method. Doesn't sound like a conspiracy to me. Just, as always, slow going.

"Using a new strategy that can rapidly generate customized RNA vaccines, MIT researchers have devised a new vaccine candidate for the Zika virus."

"However, finding a safe and effective way to deliver these vaccines has proven challenging."

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