Squalene Adjuvant (MF59) Vaxs for Bird Flu, HIV, Herpes, Hep B, HepC, Influenza, CMV

[Guest guest]

Question received..........

>Isn't Chiron the one using a flu vaccine with squalene MF59? I just came

across a flu vaccine being used in elderly with squalene.Ofcourse it is

very safe and produces a better protection rate than the flu vaccines we

currently use.

Yes M59 is in that vaccine and MF59 is squalene (similar to what has been

found in some anthrax vaccine and may be contributing or causing GWS and

other symptoms that we are seeing in military personnel who received

anthrax vaccine.

Sheri

More below.............

Squalene Adjuvant (MF59) Vaxs for Bird Flu, HIV, Herpes, Hep B, HepC,

Influenza, CMV

MF59 is a proprietary adjuvant DEVELOPED BY CHIRON

http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2 & Sect2=HITOFF & p=3 & u=%2F

netahtml%2FPTO%2Fsearch-bool.html & r=124 & f=G & l=50 & co1=AND & d=PG01 & s1='game+sho

w' & s2=children & OS=%22game+show%22+AND+children & RS=(%22game+show%22+AND+child

ren)

So far only aluminum salts and MF59 have been licensed for use as adjuvants

for formulating vaccines for application in humans

http://www.future-drugs.com/summery.asp?submit=txt2 & articleid=682 & publicatio

nid=7

MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety

profile

A Podda & G Del Giudice

Expert Review of Anti-infective Therapy 2(2),197–204 (2003)

The need to enhance the immunogenicity of purified subunit antigens has

prompted the development of several new adjuvants. However, many of these

new molecules have demonstrated a reactogenicity profile that is not

suitable for their inclusion in vaccines for human use. In this context,

the adjuvant emulsion MF59™ has been developed, tested in combination with

different antigens in several animal models and subsequently evaluated in

humans. Clinical trials with several MF59-adjuvanted vaccines have been

performed in different age groups (from newborns to the elderly) and have

shown an increased immunogenicity of coadministered antigens, associated

with a high level of safety and tolerability. MF59 has been the first

adjuvant to be licensed for human use after alum and, as part of an

enhanced influenza vaccine for the elderly, is now available in the

marketplace of several countries worldwide.

Key issues • The poor immunogenicity of recombinant and subunit antigens

requires the addition of strong and safe adjuvants to vaccine formulations.

MF59, an oil-in-water emulsion containing squalene, proved to be a powerful

adjuvant, able to enhance the immunogenicity of viral and bacterial

antigens, in several animal models. • In combination with subunit influenza

antigens, MF59 has been extensively evaluated in human clinical trials and

demonstrated not only an increased immunogenicity, but also a good safety

profile. These clinical data have led to the registration of the

MF59-adjuvanted influenza vaccine in several countries. MF59 has been the

first novel adjuvant to be licensed after aluminum salts several decades

ago. • The very good safety profile shown in younger age groups, including

infants, with other candidate vaccines adjuvanted with MF59 might pave the

way for the registration of new adjuvanted pediatric vaccines.

http://www.pasteur.fr/applications/euroconf/vaccins/vaccins-abs.html

http://www.pasteur.fr/applications/euroconf/vaccins/vaccins-abs.html#4

: " The oil/water emulsion MF59 , designed to enhance the performance of

recombinant subunit vaccines , is the first adjuvant of this type to be

approved for human use "

" The development of MF59 arose as an integral part of Chiron's commitment

to development of recombinant subunit vaccines against disease targets

which were not considered to have workable approaches with attenuated or

killed vectors. "

*******

http://www.anthrax.osd.mil/resource/qna/qaAll.asp?cID=109

Squalene in the form of an emulsion (emulsified squalene, such as an

adjuvant called MF59) has been added as an adjuvant to some investigational

vaccines in the U.S. (Burdin et al., 2004)

8) What do we know about the European influenza vaccine that uses MF59 (an

adjuvant containing squalene).

In 1997, European health agencies approved emulsified squalene (with

influenza virus in the center of each droplet) for use as an adjuvant in an

influenza vaccine (Fluad, Chiron Corporation, Marburg, Germany, and Siena,

Italy, www.forum-impfen.de/impfnavigator/packungsbeilage/5205fluad.pdf ;

Sesardic & Dobbelaer, 2004). Some clinicians consider influenza vaccine

with MF59 adjuvant to be better able to induce immunity in elderly people

(Banzhoff et al, 2003).

To make this influenza vaccine work, researchers needed a squalene

concentration of 1.95% (about 2 parts per hundred or 20 million parts per

billion) to boost the immune response. This squalene had to be in the form

of an emulsion (a mixture of tiny droplets) to be recognized by the immune

system. Squalene in its oily state is naturally present inside the human body.

Tens of millions of doses of this European influenza vaccine have been

administered safely since 1997.

http://www.nap.edu/openbook/030907178X/html/310.html

Clinical studies of MF59 and other squalene-containing adjuvants have been

conducted with candidate malaria, HSV (herpes simplex virus), HIV (human

immunodeficiency virus), and influenza vaccines (Ott et al., 1995; GAO,

1999a). Study populations for the clinical trials have included adults,

elderly, and children and infants (Ott et al., 1995).

http://www.mediscover.net/clipsdet.cfm?ClippingsId=152

However, patients who received the MF59-adjuvant vaccine had significantly

higher

geometric mean titres of antibody and seroconversion rates.

http://www.nccn.net/~wwithin/squalene.pdf

The Endogenous Adjuvant Squalene Can Induce a Chronic T-Cell-Mediated

Arthritis in Rats

Squalene is a cholesterol precursor, which stimulates the immune system

nonspecifically. We demonstrate that one intradermal injection of this

adjuvant lipid can induce joint-specific inflammation in arthritisprone DA

rats. Histopathological and immunohistochemical analyses revealed erosion

of bone and cartilage, and that development of polyarthritis coincided with

infiltration of ab1 T cells. Depletion of these cells with anti-ab TcR

monoclonal antibody (R73) resulted in complete recovery, whereas anti-

CD8 and anti-gd TcR injections were ineffective. The apparent dependence on

CD41 T cells suggested a role for genes within the major histocompatibility

complex (MHC), and this was concluded from comparative studies of MHC

congenic rat strains, in which DA.1H rats were less susceptible than DA

rats. Furthermore, LEW.1AV1 and PVG.1AV1 rats with MHC identical to DA rats

were arthritis-resistant, demonstrating that non-MHC genes also determine

susceptibility. Some of these genetic influences could be

linked to previously described arthritis susceptibility loci in an F2

intercross between DA and LEW.1AV1 ats (ie, Cia3, Oia2 and Cia5).

Interestingly, some F2 hybrid rats developed chronic arthritis, a phenotype

not apparent in the parental inbred strains. Our demonstration that an

autoadjuvant can trigger chronic, immune-mediated joint-specific

inflammation may give clues to the pathogenesis of rheumatoid arthritis,

and it raises new questions concerning the role of endogenous molecules

with adjuvant properties in chronic inflammatory diseases. (Am J Pathol

2000, 156:2057–2065)

" In conclusion, arthritis induced with the cholesterol precursor squalene

shares notable similarities with rheumatoid arthritis, and raises

interesting questions concerning the role of endogenous molecules with

adjuvant properties in chronic inflammatory diseases. "

*********

BIRD FLU vaccine

http://www.pharmacist.com/articles/h_ts_0607.cfm

Avian influenza vaccine under development

Seeking protection against pandemic, NIH awards research contract to Chiron.

" " By comparing the vaccines with and without the MF59 adjuvant, we can

determine if the adjuvant significantly augments the protective effects of

the vaccine, enabling us to use lower doses and thereby extend the vaccine

supply. "

********

Influenza Vaccine - ALREADY used

http://stg.syndnet.thomsonfn.com/InvestorRelations/PubNewsStory.aspx?partner

=5425 & storyId=74308

European Mutual Recognition Approval of Chiron's Influenza Vaccine Fluad®

Enables Launch By 2000-2001 Flu Season

Fluad is targeted to the elderly, representing the largest segment of the

influenza vaccine market. The vaccine contains Chiron's proprietary

adjuvant MF59. Adjuvants are used to boost a vaccine's effectiveness by

increasing the body's immune response. This adjuvant effect is particularly

important in elderly subjects who run a high risk of developing the most

severe influenza-related complications.

Fluad will be co-marketed in Europe by Aventis Pasteur MSD. Approval of

Fluad expands Chiron's European influenza vaccine portfolio, which includes

the highly purified sub-unit vaccine, Agrippal®, and the first

preservative-free flu vaccine Begrivac®.

http://www.asiabiotech.com/03/english/ preserved-docs/0317/0414_0416.pdf

Fluad ® was first introduced in Italy in 1997. It was the first adjuvanted

flu vaccine on the market, incorporating Chiron’s proprietary adjuvant,

MF59. ...

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg & cmd=Retrieve & db=Pu

bMed & list_uids=11425416 & dopt=AbstractLancet. 2001 Jun 16;357(9272):1937-43.

Related Articles, Links

Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza

A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential

vaccines against H5N1 influenza.

Nicholson KG, Colegate AE, Podda A, son I, Wood J, Ypma E, Zambon MC.

Infectious Diseases Unit, Leicester Royal Infirmary, LE1 5WW, Leicester,

UK. karlgnicholson@...

BACKGROUND: In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1)

viruses emerged as a pandemic threat to human beings. A non-pathogenic

variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading

vaccine candidate. We did an observer-blind, phase I, randomised trial in

healthy volunteers to assess safety, tolerability, and antigenicity of

MF59-adjuvanted and non-adjuvanted vaccines. METHODS: 32 participants were

randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given

3 weeks apart, of 7.5, 15, or 30 microg haemagglutinin surface-antigen

influenza A H5N3 vaccine. Antibody responses were measured by

haemagglutination inhibition, microneutralisation, and single radial

haemolysis (SRH). The primary outcome was geometric mean antibody titre 21

days after vaccination. FINDINGS: The A/Duck/SIngapore vaccines were safe

and well tolerated. Antibody response to non-adjuvanted vaccine was poor,

the best response occurring after two 30 microgram doses: one, four, four,

and one person of eleven seroconverted by haemagglutination inhibition,

microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric

mean titres of antibody, and seroconversion rates, were significantly

higher after MF59 adjuvanted vaccine. Two 7.5 microg doses of MF59

adjuvanted vaccine gave the highest seroconversion rates: haemagglutination

inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of

ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the

pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to

A/Duck/Singapore virus. INTERPRETATION: Non-adjuvanted A/Duck/Singapore/97

(H5N3) vaccines are poorly immunogenic and doses of 7.5-30 microg

haemagglutinin alone are unlikely to give protection from A/Hong Kong/97

(H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the

antibody response to protection levels. Our findings have implications for

development and assessment of vaccines for future pandemics.

http://www.arthritis-forum.net/arthritis/NIH_news__Avian_flu_vaccine_347908.

html

CONTRACT AWARDED TO DEVELOP VACCINE AGAINST H9N2 AVIAN INFLUENZA

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11599686 & dopt=Abstract

Eur J Epidemiol. 2001;17(2):135-40. Related Articles, Links

Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared

to a conventional subunit vaccine in elderly subjects.

Gasparini R, Pozzi T, Montomoli E, Fragapane E, Senatore F, Minutello M,

Podda A.

Institute of Hygiene, University of Siena, Italy.

Three-hundred and eight outpatient elderly subjects (> or = 65 years) were

randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLU-AD;

n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104)

in order to compare the safety and immunogenicity of the two vaccines.

Although mild pain at the injection site was reported more frequently by

subjects immunised with the adjuvanted vaccine, both vaccines were shown to

be safe and well tolerated. The adjuvanted vaccine was more immunogenic as

indicated by higher post-immunisation geometric mean titres (GMTs) and by

higher proportions of subjects with post-immunisation > or = four fold

increases of antibody titres or subjects with > or = 1/160

post-immunisation HI titres. These differences, statistically significant

for all three strains after immunisation, indicated that, by addition of

the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire

an enhanced immunogenicity without any clinically significant increase of

their reactogenicity.

****

And trials of HIV vaccines

http://home.att.net/~dstormmom/deceptn.htm

" In his AIDS work he experimented with MF59 [an adjuvant containing

squalene] because alum was destructive to HIV proteins. "

http://www.aegis.com/pubs/drugs/9.html

MTP-PE/MF59

Primary HIV-infection - as a vaccine adjuvant for enhancement of the immune

response.

*******

And trials of MF59 in Hepatitis B vaccine

( a concern I have had is that is in there already nothing the similar

responses of injury to hepatitis b vaccine and anthrax vaccine (although in

the military they get many vaccines at once including hep b vaccine)

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve &

db=PubMed & list_uids=10438046 & dopt=Abstract

Vaccine 1999 Jul 16;17(22):2769-78

A randomized, controlled study in adults of the immunogenicity of a novel

hepatitis B vaccine containing MF59 adjuvant.

Heineman TC, Clements-Mann ML, Poland GA, son RM, Izu AE, Sakamoto D,

Eiden J, Van Nest GA, Hsu HH

Division of Infectious Diseases and Immunology, St. Louis University, MO

63110-0250, USA.

[Medline record in process]

The safety and immunogenicity of a novel hepatitis B virus (HBV) vaccine

containing recombinant PreS2 and S antigens combined with MF59 adjuvant

(HBV/MF59) was evaluated in healthy adults (N=230) who were randomized to

receive 2 or 3 immunizations of either the study vaccine or a licensed

control vaccine (Recombivax HB). After a single immunization, 105 of 118

(89%) recipients of HBV/MF59 achieved protective serum levels of anti-HBs

antibody (> 10 mIU/ml), compared with 13 of 110 (12%) recipients of licensed

vaccine (P < 0.001). The geometric mean titer (GMT) after 2 doses of

HBV/MF59 given 2 months apart (13,422 mIU/ml) was more than 5-fold higher

than that following 3 doses of licensed vaccine given over 6 months (2,346

mIU/ml; P < 0.001). The GMT following 3 injections of HBV/MF59 (249,917

mIU/ml) was 100-fold higher than licensed vaccine (P < 0.001). Anti-PreS2

antibodies were elicited in over 90% of the subset of HBV/MF59 recipients

tested. Both vaccines were well tolerated; transient, mild-to-moderate local

inflammation was the major postinjection reaction.

PMID: 10438046, UI: 99364757

http://www.marketresearch.com/map/prod/714214.html

HBV vaccine/MF59 adjuvant

*******

And Hepatitis C vaccine research

http://www.hepnet.com/hepc/news21698.html Chiron again

As a result of Chiron's discovery of the hepatitis C genome in 1987, Chiron

possesses an extensive HCV patent portfolio. The proprietary vaccine

consists of a recombinant HCV antigen preparation in combination with

Chiron's MF59 adjuvant which is designed to induce viral neutralizing

antibodies as well as potentially other protective immune responses.

http://professional.cancerconsultants.com/conference_jwci_2003.aspx?id=83

Dr Houghton of Chiron Corporation presented the current status of

developing a vaccine against hepatitis C. 1 The two hepatitis C vaccine

strategies are 1) prophylactic vaccines to prevent infection and 2)

therapeutic vaccines to prevent cirrhosis and cancer. The current clinical

trial is testing a vaccine called E1E2/MF59 in chronically infected

patients. This trial is approved by NIH and FDA.

http://www.marketresearch.com/map/prod/714214.html

HCV Vaccine/MF59 adjuvant

*****

And Herpes Vaccine - HSV (Herpes Simplex) and HCV

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=10519932 & dopt=Abstract

Vaccine. 1999 Oct 14;18(5-6):434-9. Related Articles, Links

Distribution of adjuvant MF59 and antigen gD2 after intramuscular injection

in mice.

Dupuis M, Mc DM, Ott G.

Cardiovascular Research Institute and Department of Anatomy, University of

California, San Francisco, CA 94143, USA. dupuis@...

MF59, which is an adjuvant approved for human use, typically elicits higher

antibody titers than alum when used in combination with a variety of

recombinant and natural subunit antigens. The mechanisms responsible for

the adjuvant action of MF59 are not fully understood. In particular, little

is known about the in vivo distribution of MF59 and of antigen after

intramuscular (i.m.) injection. The goal of the present study was to

determine the distribution of MF59 injected with soluble antigen gD2 from

type 2 herpes simplex virus (HSV) and to compare the distribution of gD2

injected with or without MF59. At 4 h, 36% of the injected dose of labeled

MF59 was in the quadriceps muscle and about 50% was in the inguinal fat

surrounding the muscle. Half of the initial amount of labeled MF59 in

muscle was detected 42 h after injection. The amount of labeled MF59 in the

draining lymph nodes was maximal 2 d after injection, which represented

0.1-0.3% of the injected dose. At 4 h, 12% of the injected dose of labeled

gD2 was found in the muscle. The presence of MF59 did not significantly

modify the distribution of gD2. The results indicate that MF59 and gD2

distribute and are cleared independently after i.m. injection. Importantly,

MF59 is unlikely to have a repository effect, whereby it slowly releases

the antigen

http://www.racoon.com/herpes/biopage/7.html

Current Trials

Until recently, patients were enrolled in 2 competing phase III trials of

herpes simplex vaccines (Table I). Both trials were designed to test the

efficacy of recombinant subunit vaccines, one developed by Chiron

Therapeutics of Emeryville, California, and the other by Kline Beecham

of Philadelphia, Pennsylvania. Both vaccines consist of recombinant coat

proteins of the HSV-2 virion, together with an adjuvant. One difference

between the 2 vaccines is the adjuvant--Chiron uses MF59, while Kline

uses monophosphoryl lipid A immunostimulant (MPL), a bacterial product

obtained in a partnership with Ribi ImmunoChem Research, Inc., of Hamilton,

Montana. Chiron halted its trial because the initial results failed to

demonstrate the promise seen in phase I and II trials. Kline continues

to enroll patients, believing that its different adjuvant will lead to an

improvement in efficacy.

Already, the newer-generation vaccines, which often involve the

introduction of engineered DNA into the human body, are beginning clinical

trials. Some of these use traditional viral vectors, while others, termed

DNA vaccines, employ naked plasmid DNA.

http://www.annals.org/cgi/content/full/122/12/889

A Recombinant Glycoprotein Vaccine for Herpes Simplex Type 2

Objective: To evaluate the safety and immunogenicity of a recombinant

glycoprotein vaccine for herpes simplex virus type 2 (HSV-2), which

contains glycoproteins gD2 and gB2 combined with the novel MF59 adjuvant

emulsion, in HSV-2-seronegative persons

http://www.medscape.com/viewprogram/2043_pnt

The Glycoprotein Vaccine gB2D2

Chiron has investigated the glycoprotein vaccine gB2/gD2, which uses a

squalene oil-in-water emulsion adjuvant called MF59. Studies in mice showed

that the vaccine boosted HSV-specific antibody and T-cell

lymphoproliferative responses, and induced a Th2 response in mice.

******

http://www.liebertonline.com/ doi/abs/10.1089/088282403771926319

CMV vaccines

Two human cytomegalovirus (CMV) vaccines have been previously evaluated for

their

im- munogenicity: a recombinant gB/MF59 vaccine and an attenuated strain of

....

http://fiordiliji.ashley-pub.com/vl=14569957/

cl=153/nw=1/rpsv/cw/apl/14712598/v1n3/s6/p401

.... These results suggest that CMV diseases can be prevented or attenuated

and that

a vaccine combining ALVAC-CMV(pp65) with gB/MF59 may induce sufficient CTLs

and

******

http://www.bioinfo.com/aabrev98.html

Parvovirus B19 vaccine

MedImmune, Inc. concluded an agreement with Chiron Corp. for use of MF59

vaccine

adjuvant with its parvovirus B19 vaccine.

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--------------------------------------------------------

Sheri Nakken, R.N., MA, Classical Homeopath

http://www.nccn.net/~wwithin/vaccine.htm