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just point out that no DNA Vaccine, MRNA vaccine or AAV vaccine ... could ever possibly revert to virulence ... they are not based on whole virus
"will be very similar to a natural infection" ........... that is what the trial is for ? just intrigued how you knew ...
Inanaco I have years of selling these vector virus Vax so know a little about their history.
I have no intention whatsoever of engaging with you as your last advice to me was “ stay out I have sorted it out privately”. Thirty posts later still arguing about the issue that was sorted it is a complete waste of time debating with you.
what ? Ivy ... .... "not revert to virulence" ... can you explain that ???
"will be very similar to a natural infection" ...
what 100% efficacy ............ ?
Sorry for double post.Had problems with original one
As you say Bermuda the use of non replicating vector virus’s such as ChAd is very attractive to use as it means the virus will likely not revert to virulence and will be very similar to a natural infection hence stimulating a good immune response.
It would be good to get more detail on the “ sub optimal” performance in humans as that may be in part related to a lot of early work in HIV which was the initiation of these vector virus’s.
Agree we need to get better and more specific T cell responses.
However as the SCLP Vax was not included in latest WHO list it is good that the Oxford one is about to enter p3.
The SCLP one may offer better and longer protection but it is more important to get them into production for the benefit of mankind.
As you say Bermuda the use of non replicating vector virus’s such as ChAd is very attractive to use as it means the virus will likely not revert to virulence and will be very similar to a natural infection hence stimulating a good immune response.
It would be good to get more detail on the “ sub optimal” performance in humans as that may be related to
I can't open the link to Endpoints article so couldn't tell what point you were trying to make.
We'll soon find out - CanSino, AstraZeneca and Johnson & Johnson have all opted for adenovirus vectors as they generate the strongest T cell response. Assume that as both CanSino and AZN are in phase II/III trials, there have been no serious safety issues to date or the regulators wouldn't have allowed the trials to go ahead.
I'm sure that the priority for all of us is just that one/some of the vaccines actually work. Having said that, the results of many of these COVID-19 trials will shape and determine the future of new or previously unapproved tech. whether it's mRNA vaccines, type of viral vector, even DNA vaccines. It's going to be so interesting seeing how it all plays out.
i did not make any observation .... the Article did ... AAV
i just connected the pieces
Sorry Inanaco,
What point are you trying to make? Is it safety concerns surrounding adenoviral vectors?
missing "potent" ... "high Avidity" .......
Despite this promise, the efficacy of viral vectors in humans is often sub-optimal, and there is a need to develop more immunogenic vectors that elicit T cell responses not only of greater magnitude, but ideally also of the right phenotype for protection against disease.
RESEARCH AIMS
The aim of the Vector Engineering programme at the Jenner Institute is to improve adenoviruses and poxviruses as vaccine vectors. The basis for this is genetic manipulation of the vector genomes using BAC recombineering, which we developed first for MVA and have recently also applied to adenoviruses. We aim to use these reverse genetics systems to discover the factors responsible for disparities in the immunogenicity of different existing adenoviral and poxviral vectors, and to use these discoveries as a basis for rational enhancement.
Non-replicating recombinant viruses are a crucial technology in the quest for new vaccines. Used as vectors, they are able to deliver genes from a target pathogen and elicit potent B and T cell responses against the transgenic antigen. The most promising viral vaccine vectors are attenuated adenoviruses and poxviruses, including modified vaccinia virus Ankara (MVA). These are under intense investigation worldwide and are the principal platform used for vaccine development at the Jenner Institute.
Despite this promise, the efficacy of viral vectors in humans is often sub-optimal, and there is a need to develop more immunogenic vectors that elicit T cell responses not only of greater magnitude, but ideally also of the right phenotype for protection against disease. Attempts to improve viral vectors based on current immunological knowledge have been partially successful. In the Grand Challenges in Global Health project, involving screening of over 100 candidate viruses, we have achieved to date significant enhancements of CD8+ T cell responses elicited by adenovectors but with only a minority of adjuvants.
In a parallel project building on published data describing modest augmentation of MVA immunogenicity by deletion of viral genes, we have generated and tested 26 MVA mutants, some lacking multiple known immune evasion factors, but observed enhancements of only twofold at best in peak CD8+ T cell responses. These findings should have clinical utility for some diseases, but also highlight how little is known about how the immune system interacts with infectious non-replicating viruses, what factors influence the nature and magnitude of responses, and therefore how viral vectors might be improved or tailored to particular applications.
The novel replication-deficient simian adenoviral vaccine vectors ChAdOx1 and ChAdOx2 were produced by our research group and are now in use in multiple Jenner vaccine programmes.
reason why i took an interest ...
In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors because of their ability to transduce non-dividing cells, their resistance to gene silencing, and a lack of integration site preference. In this study, we utilized VSV-G pseudotype third generation lentiviral vectors harboring specific anti-tumor T-cell receptor (TCR) to establish clinical-scale lentiviral transduction of PBL. Spinoculation (1000 × g, 32°C for 2 h) in the presence of protamine sulfate represents the most efficient and economical approach to transduce a large number of PBLs compared to RetroNectin-based methods. Up to 20 million cells per well of a 6-well plate were efficiently transduced and underwent an average 50-fold expansion in two weeks. TCR transduced PBL mediated specific anti-tumor activities including IFN-? release and cell lysis. Compared to gamma-retroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population.
Keywords: Lentivirus, T-cell receptor, Adoptive immunotherapy, Gene therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399689/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548848/
also
The first patients have been dosed with ChAdOx1 nCoV-19, an adenovirus vaccine vector (AAV) developed by the Jenner Institute at the University of Oxford. It becomes the fifth COVID-19 vaccine to enter the clinic.
AAV ........................