Replies to post #14216 on Mymetics Corp (MYMX)

[Work Harder]

Per the link you posted

https://www.malariavaccine.org/projects/vaccine-projects/pfs25-vlp-and-pfs230-vlp-0

Mymetics ?

https://adisinsight.springer.com/drugs/800040913

I haven't seen it from Kempers but we are do something from him on Mararia 2nd half of 2019

[Work Harder]

Now take a look @ the illustration

in the 5th link here

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150591319

then this

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288435/

Combination eh

Here we demonstrate that combining Pfs25-IMX313

one of the TBV candidates currently in clinical development, with RTS,S/AS01 readily induces a functional immune response against both antigens in outbred CD1 mice

Maybe Kempers will clue us in

[Work Harder]

Duuno but I'd guess you can't

non cold storage AS01

[Work Harder]

Thanks Bro, that is interesting

Still would like to have a lil more clarity

[Work Harder]

The objective of this study was to shed light on whether there are other antigens that could

supersede

or

synergize

with RH5 in their ability to elicit growth-inhibitory antibodies against blood-stage

This will inform the approach taken to improve on the present RH5 vaccine and/or develop next-generation vaccine formulations targeting multiple antigens to achieve even higher levels of growth inhibitory antibodies.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558156/

[Work Harder]

Not saying it's related

but I find it interesting that an article from 2006 2008

spikes to 51 in May 2019

Comparative Testing of Six Antigen-Based Malaria Vaccine Candidates Directed Toward Merozoite-Stage Plasmodium falciparum

https://cvi.asm.org/content/15/9/1345/article-info

Refresher

Malaria Vaccines: Recent Advances and New Horizons

https://www.sciencedirect.com/science/article/pii/S1931312818303202#bib110

[Work Harder]

Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1277-x

Complement-fixing antibodies were generally relatively short-lived and were less effectively induced in older children with higher malaria exposure, which could be important for vaccine implementation in locations with high malaria transmission intensity and should be further evaluated. Furthermore, we developed statistical methods to investigate antibody decay and relationships over time post-vaccination; these approaches could be highly valuable in future vaccine trial evaluation, especially as a tool to investigate the determinants of vaccine longevity and inform strategies to improve this. Our findings support future investigation of the large phase III trials to determine whether complement fixation is a valuable correlate of protective immunity and advance the development of more efficacious and long-lasting vaccines.

[Work Harder]

By the end of 2007, Mymetics S.A., Lausanne, Switzerland took over the responsibility of this project from Pevion Biotech Ltd. PC's curent affiliation is with F. Hoffmann-La Roche Ltd., Basel, Switzerland and RZ's current affiliation is with Lonza Ltd., Visp

Rehashing the past

https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0022273

Particle-based platforms for malaria vaccines

https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1340&context=usarmyresearch

HH post

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=135747013

[Work Harder]

How could we see Results from Phase1/2 later this year?

Next steps

Mymetics is currently evaluating possible the further development of a malaria vaccine in collaboration with

PATH-MVI and LMIV.

In parallel, Mymetics is in collaboration with the

Swiss Tropical and Public Health Institute

and researchers at

Oxford University

to add two important antigens for a possible malaria vaccine candidate,

the RH5

and

the CyRPA peptides

and has received access to EU supported laboratories under the

Transvac2

program to execute the development of the tetra-valent malaria vaccine candidate

and test this in

pre-clinical studies in 2019.

https://www.sec.gov/Archives/edgar/data/927761/000165495419003503/mymx_10q.htm

Yet we have been through Phase 1

[Work Harder]

Since 2017 Mymetics is developing an improved second malaria vaccine candidate, which includes besides the existing antigens, two other possible antigens which will cover the complete life cycle of the parasite in humans. This vaccine candidate is being developed with funds from the EU and collaborations with the NIH, MVI, the

University of Oxford

and the

Swiss Tropical and Public Health institute.

Pre-clinical data is expected in the second half of 2019.

The transmission blocking malaria vaccine, is in its preclinical stage and Mymetics collaborates with the NIH and LMIV to further advance this promising vaccine. The first initial results from the study showed that the virosome vaccine candidates, at the highest dose tested, generate high antibody titers against the required antigens and they were able to significantly reduce (97-100%) the transmission of the Plasmodium falciparum parasite.

https://www.mymetics.com/vaccine-pipeline/malaria/

Goal of this project is to develop additional peptide mimetics derived from the novel blood stage antigens CyRPA and RH5 and to evaluate their protective efficacy in an innovative P. falciparum infection mouse model.

https://www.swisstph.ch/en/topics/malaria/malaria-vaccines/

Link to Project

https://www.swisstph.ch/en/projects/project-detail/project-action/detail/project-controller/Projects/project/evaluation-of-the-protective-efficacy-of-malaria-blood-stage-vaccine-condidates-in-an-innovative-p/

[Work Harder]

Just needed a ref to it so here it is

Third, wherever possible, rather than use Freund's adjuvant [a strong immunopotentiator that elicits extremely high titers of antibodies but which can also disrupt the fold of even the most stable proteins (16, 17)], we used AddaVax™, a squalene-based adjuvant similar in composition to the clinically-approved adjuvant MF59®.

Testing all 5,000 proteins encoded in the P. falciparum genome is not feasible and so in our first panel we aimed to test all of the proteins that have been the subject of promising vaccine antigen reports in the literature. We then selected a second panel, drawn from a list of 435 proteins that have been bioinformatically predicted (18) to have a role in merozoite invasion. This was 55 proteins in all. Proteins were generated for 20 of these, and then formulated in adjuvant for immunization into mice. The post-immunization mouse antibodies were harvested and then tested for activity in the GIA assay.

the authors concluded that their data "supports the good safety profile associated with MF59-adjuvanted influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines"


made acquiring this adjuvant difficult at the time of performing the study and so we examined instead AddaVax™, a preclinical analog of the licensed human adjuvant MF-59 which is a squalene-based oil-in-water emulsion (33, 34). Mice immunized with chicken egg ovalbumin (OVA) formulated with AbISCO®-100 and AddaVax™ produced comparable titers of anti-OVA serum IgG antibodies (Figure S1) and so we proceeded with AddaVax™ adjuvant for subsequent experiments.

https://en.wikipedia.org/wiki/Freund%27s_adjuvant

https://www.creative-diagnostics.com/AddaVax.htm

https://en.wikipedia.org/wiki/Squalene

It was developed in the 1990s by researchers at Ciba-Geigy and Chiron; both companies were subsequently acquired by Novartis.[13] Novartis was later acquired by CSL Bering and created the company Seqirus.

It is present in the form of an emulsion and is added to make the vaccine more immunogenic.[13] However, the mechanism of action remains unknown. MF59 is capable of switching on a number of genes that partially overlap with those activated by other adjuvants

[Work Harder]

Hmmm, whats Mario doing here

https://www.sciencedirect.com/science/article/pii/S0264410X19314380

https://www.seqirus.com/news/cell-based-seasonal-influenza-vaccines

[Work Harder]

Pandemic Influenza

MF59®-Adjuvanted Cell Culture-Derived H5N1

https://www.seqirus.com/news/options-x--conference

Influenza antigens can also be presented in the form of virosomes or can be expressed in a recombinant host (e.g., in an insect cell line using a baculovirus vector) and used in purified form (ref. 15). The invention can be used with any of these types of vaccine, but will typically be used with inactivated vaccines.

Influenza antigens can also be presented in the form of virosomes (ref. 22) (nucleic acid free viral-like liposomal particles), as in the INFLEXAL V™ and INVAVAC™ products.

http://www.freepatentsonline.com/y2018/0196061.html

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=153415328

Pevion Grants CSL Option Right to its Therapeutic Candida Vaccine

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=153381575

[Work Harder]

Rh5-CyRPA-Ripr

Whatever that is about

https://www.ncbi.nlm.nih.gov/pubmed/30542156

https://www.ncbi.nlm.nih.gov/pubmed/30965383

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007809

Influenza virus vaccine (Fluad) - Seqirus

https://adisinsight.springer.com/drugs/800013987

Adjuvants: Classification, Modus Operandi, and Licensing

https://www.hindawi.com/journals/jir/2016/1459394/

From above

https://clinicaltrials.gov/ct2/show/NCT00381875?term=NCT00381875&rank=1

MF59. MF59 is a water-in-oil squalene based emulsion that is currently licensed as part of a flu vaccine (Fluad™, Seqirus) for individuals >65 years old. Initially, the vaccine focused on elderly subjects but was later tested in the second major flu risk group, young children and infants, and was successful in both cases [30, 31]. In addition, it was also approved for the H1N1 pandemic vaccine for pregnant woman and young children [32]. Moreover, infants vaccinated with MF59-adjuvant trivalent inactivated influenza vaccine (TIV) presented higher antibody titers and polyfunctional cytokine producing CD4+ T cells than children immunized with the nonadjuvant TIV [33, 34]. The inclusion of MF59 enhanced the low effectiveness of this influenza vaccine in children under 2 years of age. Thereafter, MF59 was tested as an adjuvant for an HBV vaccine, and it was able to induce an immune response one hundred times more potent than the one induced with alum [35].
As with the majority of adjuvants, the mechanisms of action of MF59 are not fully understood. Similar to alum, MF59 effect does not rely on depot formation at the injection site, as its half-life is 42 hours [7, 36]. However, MF59 seems to be a powerful adjuvant due to its ability to induce cellular and humoral responses, including high titers of functional antibodies [37]. Indeed, MF59 is able to stimulate macrophages, resident monocytes, and DCs to secrete several chemokines like CCL4, CCL2, CCL5, and CXCL8 that in turn induce leukocyte recruitment and antigen uptake leading to migration to lymph nodes and triggering the adaptative immune response [32, 38, 39]. Systems biology studies also revealed that MF59 increases expression of the leukocyte transendothelial migration gene cluster and recruitment of MHCII+CD11b+ cells at injection site and this profile may be predictive of robust immune responses [40]. Moreover, an elegant paper by Vono and colleagues showed that transient ATP release is required for innate and adaptive immune responses induced by MF59 [41].

[Work Harder]

For rabbit and rat immunization, Freund's adjuvant was used to allow comparison with other studies. For S-Antigen-BAP-Strep and AARP-BAP-Strep rabbit immunization, Zika rabbits were injected intramuscularly

by Biogenes (Germany).

For Zika rabbits, each 400 µL dose consisted of 200 µL of protein solution at 0.5 mg/mL (100 µg dose) and 200 µL of complete Freund's adjuvant (day 1) or incomplete Freund's adjuvant (days 28 and 56). For CyRPA rabbit immunization, New Zealand White rabbits were immunized by Cambridge Research Biochemicals (UK). For these rabbits, each 400 µL dose consisted of 200 µL of protein solution at 0.5 mg/mL (100 µg dose) and 200 µL AddaVax™ adjuvant (Invivogen, France), on days 1, 28, and 56. For all rabbits the final bleed was day 63, 1 week after the final immunization. For CyRPA rat immunization, 2 Sprague-Dawley, and 2 Wistar rats were immunized intramuscularly by GenScript (Hong Kong) with 50 µg of protein formulated with complete Freund's adjuvant (day 1) and incomplete Freund's adjuvant (days 28 and 56). Rat serum was harvested on day 70 and IgG purified.

Both studies used very similar immunogens and also the same contractor for rabbit immunization (Cambridge Research Biochemicals)

https://www.biogenes.de/

In addition to the Welcome Trust

This work was supported in-part by funding from the European Union's Horizon 2020 research and innovation programme under grant agreement for OptiMalVax [number 733273

http://webcache.googleusercontent.com/search?q=cache:ck27YcN8KR4J:www.optimalvax.eu/objectives/+&cd=1&hl=en&ct=clnk&gl=us

n order to develop an appropriate multi-stage malaria vaccine we will:
–Find the two best malaria vaccine antigen candidates for each malaria stage:
Sporozoite
Liver-stage
Blood-stage
Sexual stage
–Find the best virus-like particle (VLP) to present three of the above
–Conduct GMP manufacture of two new bivalent VLPs and a new clinical adjuvant
–Conduct clinical trials of the best malaria vaccine candidates for the malaria stages:
Pre-erythrocytic
Blood-stage
Sexual-stage


This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733273

http://webcache.googleusercontent.com/search?q=cache:5SN8Gp8HvSUJ:www.optimalvax.eu/strategy/+&cd=2&hl=en&ct=clnk&gl=us

https://cordis.europa.eu/project/id/733273