Yksinomaan antigeenien varaan pohjautuvat rokotteet eivät välttämättä anna riittävää suojaa. Tarvitaan lisätekijöitä jotka auttavat immuunijärjestelmää tunnistamaan ja tuhoamaan taudinaiheuttajat tehokkaammin. Parhaillaan on kehitteillä tuberkuloosirokote jossa käytetään lisätekijää nimeltään IC31(R). Lupaavina kandidaatteina ovat myös esim. Borrelia spp, S.pneumoniae jne.
Ps. Aiemmat borreliarokotekokeilut ovat epäonnistuneet. Osa rokotteita saaneista sairastui borrelioosiin vakavasti.
"Vaccines, based on antigens alone, are not always sufficient to provide full protection. Adjuvants are needed to educate the immune system to recognize and eliminate the pathogens efficiently"
"IC31(R) is an adjuvant that induces T-cell and B-cell responses by using a unique synthetic formulation which combines the immunostimulating properties of an anti-microbial peptide, KLK, and an immunostimulatory oligodeoxynucleotide, ODN1a."
"Intercell currently uses IC31(R) in collaborations with a number of global vaccine companies and biotech companies. These collaborations include amongst others the development of a tuberculosis vaccine in Phase I clinical trials, which has been partnered with the Danish Statens Serum Institut and Sanofi Pasteur."
"The most promising candidates are validated. AIP(R) has successfully been applied to identify a large number of novel antigens from numerous pathogenic organisms including S. aureus, S. epidermidis, S. pneumoniae, S. agalactiae, S. pyogenes, E. faecalis, K. pneumoniae, Borrelia spp., ETEC, Shigella, C. jejuni, non-typeable H. influenzae and M. catarrhalis. It has resulted in promising in-house product candidates and generated strategic partnerships."
http://news.prnewswire.com/DisplayRelea ... 141&EDATE=
BORRELIOOSIROKOTE
Valvojat:Jatta1001, Borrelioosiyhdistys, Waltari, Bb
Baxterin borrelioosirokote Eurooppaan ja USA:an:
Search Results[PPT] Lyme Borreliosis VaccineFile Format: Microsoft Powerpoint - View as HTML
OspA Vaccine Strategy. 4. B i o S c i e n c e. Structure of native and type 1/2 OspA ...Baxter data ; 75% B. garinii, 25% B. burgdorferi s.s. + B. afzelii ...
http://www.paru.cas.cz/ICTTD_Bioinforma ... Materials/ Wed%20Livey%20Bb%20Vaccine.ppt
http://74.125.77.132/search?q=cache:LbD ... cd=1&gl=fi
Search Results[PPT] Lyme Borreliosis VaccineFile Format: Microsoft Powerpoint - View as HTML
OspA Vaccine Strategy. 4. B i o S c i e n c e. Structure of native and type 1/2 OspA ...Baxter data ; 75% B. garinii, 25% B. burgdorferi s.s. + B. afzelii ...
http://www.paru.cas.cz/ICTTD_Bioinforma ... Materials/ Wed%20Livey%20Bb%20Vaccine.ppt
http://74.125.77.132/search?q=cache:LbD ... cd=1&gl=fi
Koirille kehitetty borrelioosirokote nimeltään Nobivac Lyme. Rokote vaikuttaa kahteen pintaproteiiniin. Rokotteen kerrotaan olevan huomattava edistysaskel borrelioosirokotteiden saralla koirilla sillä toisista rokotteista poiketen se sisältää OspC vasta-aineita jotka tuhoavat borreliabakteerin infektion eri vaiheissa.:
http://www.dogchannel.com/dog-news/2009 ... duced.aspx
New Lyme Vaccine for Dogs Introduced
Vaccine targets two key outer surface proteins involved in the disease?s transmission.
Posted: June 22, 2009, 5 a.m. EDT
Intervet/Schering-Plough Animal Health recently introduced Nobivac Lyme, a vaccine designed to provide dogs with dual protection against Lyme disease.
The vaccine targets two key outer surface proteins involved in the transmission of canine Lyme disease, according to the Kenilworth, N.J.-based company. It induces the production of highly specific antibodies, called borreliacidal antibodies, which killBorrelia burgdorferi (the causative agent of Lyme disease) by binding to outer surface proteins (Osp) A and C. Other available products only protect against OspA, according to Rhonda LaFleur, Ph.D., group leader, Biologicals Research and Development at Intervet/Schering-Plough Animal Health.
?This vaccine represents a major advance in the prevention of Lyme disease in dogs because, unlike other Lyme vaccines on the market, it induces OspC borreliacidal antibodies that can kill B. burgdorferi at multiple time points during the infection process,? Dr. LaFleur said. ?OspA borreliacidal antibodies only kill Borrelia while they are in the tick midgut. OspC borreliacidal antibodies, however, kill spirochetes in the tick midgut, spirochetes that are migrating from the midgut to the tick?s salivary glands and spirochetes that are introduced into the dog.?
Nobivac Lyme is administered by giving two doses subcutaneously, two to four weeks apart, with an annual booster thereafter. The company reported that safety studies demonstrated virtually no site reactions.
The clinical signs of Lyme disease range from subtle lameness to high fever, swollen lymph nodes, lameness and loss of appetite. Rarely, a dog infected with the disease can develop severe clinical signs that, if left untreated or treated too late, can result in permanent damage to the heart, kidneys, nervous system and joints, or can even be fatal.
http://www.dogchannel.com/dog-news/2009 ... duced.aspx
New Lyme Vaccine for Dogs Introduced
Vaccine targets two key outer surface proteins involved in the disease?s transmission.
Posted: June 22, 2009, 5 a.m. EDT
Intervet/Schering-Plough Animal Health recently introduced Nobivac Lyme, a vaccine designed to provide dogs with dual protection against Lyme disease.
The vaccine targets two key outer surface proteins involved in the transmission of canine Lyme disease, according to the Kenilworth, N.J.-based company. It induces the production of highly specific antibodies, called borreliacidal antibodies, which killBorrelia burgdorferi (the causative agent of Lyme disease) by binding to outer surface proteins (Osp) A and C. Other available products only protect against OspA, according to Rhonda LaFleur, Ph.D., group leader, Biologicals Research and Development at Intervet/Schering-Plough Animal Health.
?This vaccine represents a major advance in the prevention of Lyme disease in dogs because, unlike other Lyme vaccines on the market, it induces OspC borreliacidal antibodies that can kill B. burgdorferi at multiple time points during the infection process,? Dr. LaFleur said. ?OspA borreliacidal antibodies only kill Borrelia while they are in the tick midgut. OspC borreliacidal antibodies, however, kill spirochetes in the tick midgut, spirochetes that are migrating from the midgut to the tick?s salivary glands and spirochetes that are introduced into the dog.?
Nobivac Lyme is administered by giving two doses subcutaneously, two to four weeks apart, with an annual booster thereafter. The company reported that safety studies demonstrated virtually no site reactions.
The clinical signs of Lyme disease range from subtle lameness to high fever, swollen lymph nodes, lameness and loss of appetite. Rarely, a dog infected with the disease can develop severe clinical signs that, if left untreated or treated too late, can result in permanent damage to the heart, kidneys, nervous system and joints, or can even be fatal.
Viidelle henkilölle kehittyi neuropatia (= tunto/liikehermojen vioittuminen) heidän saatuaan vesirokko-, vesikauhu- tai borrelioosirokotteen. Oireet alkoivat vuorokaudesta kahteen kuukautta rokotteen annosta. Oire kroonistui. (2009)
Vaccine. 2009 Oct 3; [Epub ahead of print] Small fiber neuropathy following vaccination for rabies, varicella or Lymedisease. Souayah N, Ajroud-Driss S, Sander HW, Brannagan TH, Hays AP, Chin RL. Department of Neurology, New Jersey Medical School, 90 Bergen Street, DOC 8100,Newark, NJ 07103, United States.
Neuropathy following vaccination has been reported; however, biopsy-confirmedsmall fiber neuropathy has not been described. We report five patients whodeveloped paresthesias within one day to two months following vaccination for rabies, varicella zoster, or Lyme disease. On examination, there was mild sensory loss in distal extremities, preserved strength, normal or minimallyabnormal electrodiagnostic findings, and decreased epidermal nerve fiberdensities per skin biopsy. Empiric immunomodulatory therapy was tried in twopatients and was ineffective. All patients' symptoms have improved, but persist.We conclude that an acute or subacute, post-vaccination small fiber neuropathymay occur and follow a chronic course.
http://eutils.ncbi.nlm.nih.gov/entrez/e ... rlinksPMID: 19808027 [PubMed - as supplied by publisher]
Vaccine. 2009 Oct 3; [Epub ahead of print] Small fiber neuropathy following vaccination for rabies, varicella or Lymedisease. Souayah N, Ajroud-Driss S, Sander HW, Brannagan TH, Hays AP, Chin RL. Department of Neurology, New Jersey Medical School, 90 Bergen Street, DOC 8100,Newark, NJ 07103, United States.
Neuropathy following vaccination has been reported; however, biopsy-confirmedsmall fiber neuropathy has not been described. We report five patients whodeveloped paresthesias within one day to two months following vaccination for rabies, varicella zoster, or Lyme disease. On examination, there was mild sensory loss in distal extremities, preserved strength, normal or minimallyabnormal electrodiagnostic findings, and decreased epidermal nerve fiberdensities per skin biopsy. Empiric immunomodulatory therapy was tried in twopatients and was ineffective. All patients' symptoms have improved, but persist.We conclude that an acute or subacute, post-vaccination small fiber neuropathymay occur and follow a chronic course.
http://eutils.ncbi.nlm.nih.gov/entrez/e ... rlinksPMID: 19808027 [PubMed - as supplied by publisher]
Yalen tutkijat ovat huomanneet että punkin syljessä oleva proteiini suojelee hiiriä borrelioosiin sairastumiselta. Havainto saattaa auttaa uuden borrelioosirokotteen kehittelyssä.
On the Trail of a Vaccine for Lyme Disease: Yale Researchers Target Tick Saliva
http://opa.yale.edu/news/article.aspx?id=7083
Published: November 18, 2009
New Haven, Conn. ? A protein found in the saliva of ticks helps protect mice from developing Lyme disease, Yale researchers have discovered. The findings, published in the November 19 issue of Cell Host & Microbe, may spur development of a new vaccine against infection from Lyme disease, which is spread through tick bites.
Traditionally, vaccines have directly targeted specific pathogens. This is the first time that antibodies against a protein in the saliva of a pathogen?s transmitting agent (in this case, the tick) has been shown to confer immunity when administered protectively as a vaccine.
On the Trail of a Vaccine for Lyme Disease: Yale Researchers Target Tick Saliva
http://opa.yale.edu/news/article.aspx?id=7083
Published: November 18, 2009
New Haven, Conn. ? A protein found in the saliva of ticks helps protect mice from developing Lyme disease, Yale researchers have discovered. The findings, published in the November 19 issue of Cell Host & Microbe, may spur development of a new vaccine against infection from Lyme disease, which is spread through tick bites.
Traditionally, vaccines have directly targeted specific pathogens. This is the first time that antibodies against a protein in the saliva of a pathogen?s transmitting agent (in this case, the tick) has been shown to confer immunity when administered protectively as a vaccine.
Uusin rokote kehitteillä: Tutkijat yrittävät nyt estää uudet tartunnat kytkemällä bakteerista pois päältä ne geenit jotka mahdollistavat infektion syntymisen. ILADSin entisen puheenjohtajan tri Strickerin mukaan tutkimus on ehdottomasti lisätutkimusten arvoinen mutta rokotteen turvallisuuteen tulee kiinnittää erityistä huomiota. (2010)
Genetic Engineering Raises Hope for Lyme Disease Vaccine
Researcher describes finding as a theory that still needs testing
Posted: April 5, 2010
Related Articles
By Alan Mozes
HealthDay Reporter
MONDAY, April 5 (HealthDay News) -- In an effort to combat Lyme disease, researchers have found that tick-borne transmission might be preventable by deactivating a key gene in the bacteria that enables infection.
Though to date the strategy has been tested solely in mice, theoretically the discovery could lead toward development of a vaccine that reduces the risk for infection.
"Certain genes are activated by the bacteria that causes Lyme disease during tick feeding, and for the first time we found the one that is absolutely necessary to transmit infection," said the study's lead author, Robert D. Gilmore Jr., a research microbiologist and head of the molecular and cellular microbiology lab in the bacterial diseases branch at the U.S. Centers for Disease Control and Prevention in Fort Collins, Colo.
Their findings are published in the April 5-9 online edition of the Proceedings of the National Academy of Sciences.
Lyme disease is transmitted by the bite of a black-legged tick infected with the Borrelia burgdorferi bacteria, according to the CDC. If caught early, the agency notes, a regimen of antibiotics can successfully tackle the disease in most cases. But if symptoms -- which include fever, headache, chills, a rash, muscle and joint aches and fatigue -- are not swiftly diagnosed and treatment started, Lyme disease can move across a person's joints, heart and nervous system.
In some instances, the ensuing infectious spread can provoke a host of problems, including severe joint pain and swelling, stiffness, heart palpitations, dizziness and a broad range of neurological issues. The exact mechanism underlying such long-term complications remains unclear, but some research has suggested that they might be the result of a compromised autoimmune response.
To cut Lyme disease off at the pass, Gilmore and his team set out to disrupt transmission at the genetic level. They homed in on the bacteria's "bba64" gene, which had been identified in earlier research, and genetically altered the bacteria to disable the gene. After injecting the reengineered bacteria into test mice, they allowed black-legged ticks to feed on the inoculated rodents.
In turn, a separate batch of 15 healthy mice was exposed to the ticks, which were newly infected with the altered bacterial strain.
After exposure to the altered bacteria-carrying ticks for about two months, just two of the mice had acquired Lyme disease, the study authors found.
The researchers then extracted the altered bacteria from the same ticks and injected it directly into healthy mice. They found that when injected with the altered bacteria -- rather than having been bitten by ticks that carried it -- healthy mice did, in fact, acquire Lyme disease.
This led the scientists to conclude that the altered bacteria could still prompt Lyme disease, but, as a practical matter, the disease could not be transmitted via normal tick bites when the bba64 gene was rendered nonfunctional.
"Now that we've targeted something that seems to be important in transmission, the logical thing would be to go ahead and see if it would work as a vaccine candidate," Gilmore explained.
"But I want to be clear that we have not yet done that," he cautioned. "And when you find genes that could be targeted for intervention strategies, it doesn't mean that it's going to work. It's an idea that now we have to test out."
Dr. Raphael B. Stricker, an attending physician at the California Pacific Medical Center in San Francisco and past president of the International Lyme and Associated Diseases Society, described the current effort as a "really sophisticated approach" to combating Lyme disease.
"The notion that you can specifically block infection by blocking or knocking out this gene is very interesting from a basic science point of view," Stricker said. "But I don't really know how this is going to translate into a vaccine, which is the point of this study. And I would be concerned about the safety of this kind of vaccine," he noted.
"But it's absolutely worth further investigation," he added. "And I would say that, if it would be safe, I think it would be very productive."
Genetic Engineering Raises Hope for Lyme Disease Vaccine
Researcher describes finding as a theory that still needs testing
Posted: April 5, 2010
Related Articles
By Alan Mozes
HealthDay Reporter
MONDAY, April 5 (HealthDay News) -- In an effort to combat Lyme disease, researchers have found that tick-borne transmission might be preventable by deactivating a key gene in the bacteria that enables infection.
Though to date the strategy has been tested solely in mice, theoretically the discovery could lead toward development of a vaccine that reduces the risk for infection.
"Certain genes are activated by the bacteria that causes Lyme disease during tick feeding, and for the first time we found the one that is absolutely necessary to transmit infection," said the study's lead author, Robert D. Gilmore Jr., a research microbiologist and head of the molecular and cellular microbiology lab in the bacterial diseases branch at the U.S. Centers for Disease Control and Prevention in Fort Collins, Colo.
Their findings are published in the April 5-9 online edition of the Proceedings of the National Academy of Sciences.
Lyme disease is transmitted by the bite of a black-legged tick infected with the Borrelia burgdorferi bacteria, according to the CDC. If caught early, the agency notes, a regimen of antibiotics can successfully tackle the disease in most cases. But if symptoms -- which include fever, headache, chills, a rash, muscle and joint aches and fatigue -- are not swiftly diagnosed and treatment started, Lyme disease can move across a person's joints, heart and nervous system.
In some instances, the ensuing infectious spread can provoke a host of problems, including severe joint pain and swelling, stiffness, heart palpitations, dizziness and a broad range of neurological issues. The exact mechanism underlying such long-term complications remains unclear, but some research has suggested that they might be the result of a compromised autoimmune response.
To cut Lyme disease off at the pass, Gilmore and his team set out to disrupt transmission at the genetic level. They homed in on the bacteria's "bba64" gene, which had been identified in earlier research, and genetically altered the bacteria to disable the gene. After injecting the reengineered bacteria into test mice, they allowed black-legged ticks to feed on the inoculated rodents.
In turn, a separate batch of 15 healthy mice was exposed to the ticks, which were newly infected with the altered bacterial strain.
After exposure to the altered bacteria-carrying ticks for about two months, just two of the mice had acquired Lyme disease, the study authors found.
The researchers then extracted the altered bacteria from the same ticks and injected it directly into healthy mice. They found that when injected with the altered bacteria -- rather than having been bitten by ticks that carried it -- healthy mice did, in fact, acquire Lyme disease.
This led the scientists to conclude that the altered bacteria could still prompt Lyme disease, but, as a practical matter, the disease could not be transmitted via normal tick bites when the bba64 gene was rendered nonfunctional.
"Now that we've targeted something that seems to be important in transmission, the logical thing would be to go ahead and see if it would work as a vaccine candidate," Gilmore explained.
"But I want to be clear that we have not yet done that," he cautioned. "And when you find genes that could be targeted for intervention strategies, it doesn't mean that it's going to work. It's an idea that now we have to test out."
Dr. Raphael B. Stricker, an attending physician at the California Pacific Medical Center in San Francisco and past president of the International Lyme and Associated Diseases Society, described the current effort as a "really sophisticated approach" to combating Lyme disease.
"The notion that you can specifically block infection by blocking or knocking out this gene is very interesting from a basic science point of view," Stricker said. "But I don't really know how this is going to translate into a vaccine, which is the point of this study. And I would be concerned about the safety of this kind of vaccine," he noted.
"But it's absolutely worth further investigation," he added. "And I would say that, if it would be safe, I think it would be very productive."
Borreliatartunnalta on vaikea suojautua riittävän tehokkaasti; vaatetus, karkotteet, nurmikon leikkaus jne. Rokotteita on vuosien ajan yritetty kehittää ja yksi oli markkinoillakin jonkin aikaa mutta rokotteen seurauksena useat henkilöt sairastuivat vakavaan Borrelioosiin ja se
jouduttiin vetämään pois markkinoilta.
Alla rokotteen kehittelyn tärkeyttä käsittelevä artikkeli.
Clin Infect Dis. 2011 Feb;52 Suppl 3:s247-52.
The Lyme disease vaccine--a public health perspective.
Shen AK, Mead PS, Beard CB.
Department of Health and Human Services, Washington, DC, USA.
Lyme disease, which is caused by the spirochetal agent Borrelia burgdoferi, is
the most common vector-borne illness in the United States. In 1998, the US Food
and Drug Administration approved a recombinant Lyme disease vaccine that was
later voluntarily withdrawn from the market by the manufacturer. Current Lyme
disease prevention efforts focus on a combination of methods and approaches,
including area acaricides, landscape management, host-targeted interventions,
management of deer populations, and personal protective measures, such as the
use of insect repellant and tick checks. Although these methods are generally
safe and relatively inexpensive, the primary limitations of these methods are
that their effectiveness has been difficult to demonstrate conclusively and that
rates of compliance are generally poor. An effective human Lyme disease vaccine
that has been adequately evaluated in the highest-risk population groups could
be very beneficial in preventing Lyme disease; however, it would need to meet
high standards regarding safety, efficacy, cost, and public acceptance.
Publication Types:
Research Support, Non-U.S. Gov't
http://eutils.ncbi.nlm.nih.gov/entrez/e ... md=prlinks
PMID: 21217171 [PubMed - in process]
jouduttiin vetämään pois markkinoilta.
Alla rokotteen kehittelyn tärkeyttä käsittelevä artikkeli.
Clin Infect Dis. 2011 Feb;52 Suppl 3:s247-52.
The Lyme disease vaccine--a public health perspective.
Shen AK, Mead PS, Beard CB.
Department of Health and Human Services, Washington, DC, USA.
Lyme disease, which is caused by the spirochetal agent Borrelia burgdoferi, is
the most common vector-borne illness in the United States. In 1998, the US Food
and Drug Administration approved a recombinant Lyme disease vaccine that was
later voluntarily withdrawn from the market by the manufacturer. Current Lyme
disease prevention efforts focus on a combination of methods and approaches,
including area acaricides, landscape management, host-targeted interventions,
management of deer populations, and personal protective measures, such as the
use of insect repellant and tick checks. Although these methods are generally
safe and relatively inexpensive, the primary limitations of these methods are
that their effectiveness has been difficult to demonstrate conclusively and that
rates of compliance are generally poor. An effective human Lyme disease vaccine
that has been adequately evaluated in the highest-risk population groups could
be very beneficial in preventing Lyme disease; however, it would need to meet
high standards regarding safety, efficacy, cost, and public acceptance.
Publication Types:
Research Support, Non-U.S. Gov't
http://eutils.ncbi.nlm.nih.gov/entrez/e ... md=prlinks
PMID: 21217171 [PubMed - in process]
Borrelioosirokotteet; Mitä tapahtui ja mitä olemme oppineet aiemmista kokemuksista? Artikkelissa tarkastellaan vaikeuksia kehittää tehokas, riskitön borreliarokote.
Clin Infect Dis. 2011 Feb;52 Suppl 3:s253-8.
Vaccines against Lyme disease: What happened and what lessons can we learn?
Poland GA.
Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
55905, USA.poland.gregory@mayo.edu
This article reviews events that led to the withdrawal of the only vaccine to
prevent Lyme disease licensed in the United States. The primary issues that led
to the vaccine's withdrawal appear to be a combination of vaccine safety
concerns, sparked by a molecular mimicry hypothesis that suggested that the
vaccine antigen, outer surface protein A, serves as an autoantigen and hence was
arthritogenic; concerns raised by anti-vaccine groups regarding vaccine safety;
vaccine cost; a difficult vaccination schedule and the potential need for
boosters; class action lawsuits; uncertainty regarding risk of disease; and low
public demand. This article reviews lessons learned from these events and
proposes that future candidate Lyme disease vaccines are unlikely to be
developed, tested, and used within the United States in the near future, thus
leaving at-risk populations unprotected.
Publication Types:
Research Support, Non-U.S. Gov't
http://eutils.ncbi.nlm.nih.gov/entrez/e ... md=prlinks
PMID: 21217172 [PubMed - in process]
Clin Infect Dis. 2011 Feb;52 Suppl 3:s253-8.
Vaccines against Lyme disease: What happened and what lessons can we learn?
Poland GA.
Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
55905, USA.poland.gregory@mayo.edu
This article reviews events that led to the withdrawal of the only vaccine to
prevent Lyme disease licensed in the United States. The primary issues that led
to the vaccine's withdrawal appear to be a combination of vaccine safety
concerns, sparked by a molecular mimicry hypothesis that suggested that the
vaccine antigen, outer surface protein A, serves as an autoantigen and hence was
arthritogenic; concerns raised by anti-vaccine groups regarding vaccine safety;
vaccine cost; a difficult vaccination schedule and the potential need for
boosters; class action lawsuits; uncertainty regarding risk of disease; and low
public demand. This article reviews lessons learned from these events and
proposes that future candidate Lyme disease vaccines are unlikely to be
developed, tested, and used within the United States in the near future, thus
leaving at-risk populations unprotected.
Publication Types:
Research Support, Non-U.S. Gov't
http://eutils.ncbi.nlm.nih.gov/entrez/e ... md=prlinks
PMID: 21217172 [PubMed - in process]
Lääkeyhtiö Baxter (Itävalta) yrittää kehittää borrelioosirokotetta.
Clin Infect Dis. 2011 Feb;52 Suppl 3:s266-70.
A new approach to a Lyme disease vaccine.
Livey I, O'Rourke M, Traweger A, Savidis-Dacho H, Crowe BA, Barrett PN, Yang X,
Dunn JJ, Luft BJ.
Baxter Innovations GmbH, Biomedical Research Center, Orth an der Donau, Austria.
ian.livey@baxter.com
A single recombinant outer surface protein A (OspA) antigen designed to contain
protective elements from 2 different OspA serotypes (1 and 2) is able to induce
antibody responses that protect mice against infection with either Borrelia
burgdorferi sensu stricto (OspA serotype-1) or Borrelia afzelii (OspA
serotype-2). Protection against infection with B burgdorferi ss strain ZS7 was
demonstrated in a needle-challenge model. Protection against B. afzelii species
was shown in a tick-challenge model using feral ticks. In both models, as little
as .03 mug of antigen, when administered in a 2-dose immunization schedule with
aluminum hydroxide as adjuvant, was sufficient to provide complete protection
against the species targeted. This proof of principle study proves that
knowledge of protective epitopes can be used for the rational design of
effective, genetically modified vaccines requiring fewer OspA antigens and
suggests that this approach may facilitate the development of an OspA vaccine
for global use.
Publication Types:
Research Support, Non-U.S. Gov't
http://eutils.ncbi.nlm.nih.gov/entrez/e ... md=prlinks
PMID: 21217174 [PubMed - in process]
Clin Infect Dis. 2011 Feb;52 Suppl 3:s266-70.
A new approach to a Lyme disease vaccine.
Livey I, O'Rourke M, Traweger A, Savidis-Dacho H, Crowe BA, Barrett PN, Yang X,
Dunn JJ, Luft BJ.
Baxter Innovations GmbH, Biomedical Research Center, Orth an der Donau, Austria.
ian.livey@baxter.com
A single recombinant outer surface protein A (OspA) antigen designed to contain
protective elements from 2 different OspA serotypes (1 and 2) is able to induce
antibody responses that protect mice against infection with either Borrelia
burgdorferi sensu stricto (OspA serotype-1) or Borrelia afzelii (OspA
serotype-2). Protection against infection with B burgdorferi ss strain ZS7 was
demonstrated in a needle-challenge model. Protection against B. afzelii species
was shown in a tick-challenge model using feral ticks. In both models, as little
as .03 mug of antigen, when administered in a 2-dose immunization schedule with
aluminum hydroxide as adjuvant, was sufficient to provide complete protection
against the species targeted. This proof of principle study proves that
knowledge of protective epitopes can be used for the rational design of
effective, genetically modified vaccines requiring fewer OspA antigens and
suggests that this approach may facilitate the development of an OspA vaccine
for global use.
Publication Types:
Research Support, Non-U.S. Gov't
http://eutils.ncbi.nlm.nih.gov/entrez/e ... md=prlinks
PMID: 21217174 [PubMed - in process]
Re: BORRELIOOSIROKOTE
(Lancet 2013) Lääkelaitos Baxterin rahoittama tutkimus jossa kehitellään borrelioosirokotetta USA:n ja Euroopan markkinoille.
Rokotetta on alustavasti tutkittu Euroopassa 2011 - 2012. Rokote saattaa olla soveltuva Borrelioosiin mutta lisätutkimuksia tarvitaan.
The Lancet Infectious Diseases, Early Online Publication, 10 May 2013
doi:10.1016/S1473-3099(13)70110-5Cite or Link Using DOI
This article can be found in the following collections: Infectious Diseases (Immunisation & vaccination, Neurological infections); Neurology (Neurological infections)
Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial
Nina Wressnigg PhD a, Eva-Maria Pöllabauer MD a, Gerald Aichinger MD a, Daniel Portsmouth PhD c, Alexandra Löw-Baselli PhD a, Sandor Fritsch PhD b, Ian Livey PhD c, Brian A Crowe PhD c, Michael Schwendinger PhD c, Peter Brühl PhD c, Andreas Pilz PhD c, Thomas Dvorak PhD b, Julia Singer PhD b, Clair Firth MSc b, Prof Benjamin Luft MD d, Bernhard Schmitt MD e, Markus Zeitlinger MD f, Prof Markus Müller MD f, Prof Herwig Kollaritsch MD f, Maria Paulke-Korinek MD f, Meral Esen MD g, Prof Peter G Kremsner MD g, Hartmut J Ehrlich MD b, Dr P Noel Barrett PhD c
Summary
Background
Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults.
Methods
Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18—70 years who were seronegative for B burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 μg, 60 μg, or 90 μg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9—12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1—6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347.
Findings
300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 μg, 51 to 60 μg, and 50 to 90 μg doses), and 149 to non-adjuvanted vaccines (50 to 30 μg, 49 to 60 μg, and 50 to 90 μg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41—0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13—0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 μg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4—20] of 50), injection-site pain (16 [32%, 21—45]), and tenderness (17 [34%, 23—47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1—6 after the first three vaccinations (range 6944—17 321) and booster (19 056—32 824) immunisations. The 30 μg adjuvanted formulation induced the highest antibody titres after the booster: range 26 143 (95% CI 18 906—36 151) to 42 381 (31 288—57 407).
Interpretation
The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin.
Funding
Baxter.
Rokotetta on alustavasti tutkittu Euroopassa 2011 - 2012. Rokote saattaa olla soveltuva Borrelioosiin mutta lisätutkimuksia tarvitaan.
The Lancet Infectious Diseases, Early Online Publication, 10 May 2013
doi:10.1016/S1473-3099(13)70110-5Cite or Link Using DOI
This article can be found in the following collections: Infectious Diseases (Immunisation & vaccination, Neurological infections); Neurology (Neurological infections)
Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial
Nina Wressnigg PhD a, Eva-Maria Pöllabauer MD a, Gerald Aichinger MD a, Daniel Portsmouth PhD c, Alexandra Löw-Baselli PhD a, Sandor Fritsch PhD b, Ian Livey PhD c, Brian A Crowe PhD c, Michael Schwendinger PhD c, Peter Brühl PhD c, Andreas Pilz PhD c, Thomas Dvorak PhD b, Julia Singer PhD b, Clair Firth MSc b, Prof Benjamin Luft MD d, Bernhard Schmitt MD e, Markus Zeitlinger MD f, Prof Markus Müller MD f, Prof Herwig Kollaritsch MD f, Maria Paulke-Korinek MD f, Meral Esen MD g, Prof Peter G Kremsner MD g, Hartmut J Ehrlich MD b, Dr P Noel Barrett PhD c
Summary
Background
Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults.
Methods
Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18—70 years who were seronegative for B burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 μg, 60 μg, or 90 μg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9—12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1—6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347.
Findings
300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 μg, 51 to 60 μg, and 50 to 90 μg doses), and 149 to non-adjuvanted vaccines (50 to 30 μg, 49 to 60 μg, and 50 to 90 μg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41—0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13—0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 μg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4—20] of 50), injection-site pain (16 [32%, 21—45]), and tenderness (17 [34%, 23—47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1—6 after the first three vaccinations (range 6944—17 321) and booster (19 056—32 824) immunisations. The 30 μg adjuvanted formulation induced the highest antibody titres after the booster: range 26 143 (95% CI 18 906—36 151) to 42 381 (31 288—57 407).
Interpretation
The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin.
Funding
Baxter.
Re: BORRELIOOSIROKOTE
Borrelioosirokote saattaa olla todellisuutta muutaman vuoden kuluttua. "Emme tiedä vielä kuinka tehokas rokote on, mutta se vaikuttaa lupaavalta. Tutkimuksen seuraavassa vaiheessa sitä testataan suuremmalla tutkimusjoukolla." (Infektiolääkäri, dosentti Rolf Gustafsson)
Rokotteen kehittelyn ongelmana on ollut borreliabakteerin kyky muuntua jatkuvasti ja siten estää esim. immuunipuolustusta havaitsemasta sitä. Uusi rokote on kuitenkin kehitetty siten että se suojaa borreliabakteerilta ihmisruumiin ulkopuolella eli rokotteen seurauksena muodostuneet vasta-aineet hyökkäävät bakteeria vastaan siinä vaiheessa kun punkki puree henkilöä eivätkä bakteerit siksi pääse etenemään elimistöön. Rokote perustuu siten aivan uudenlaiseen lähestymistapaan.
Tähän mennessä rokotteen sivuvaikutuksina on ilmennyt lievää kipua, punoitusta ja turvotusta. Rokote saattaa olla valmis vuoteen 2018 mennessä. Rokotteita tarvitaan useita; ensimmäisen vuoden aikana 3 ja sen jälkeen tehostrokote 3 vuoden välein.
Tähän mennessä rokotteen on saanut ainoastaan 300 henkilöä. V. 2015 tutkimusjoukko käsittää 10 000 henkilöä Ruotsissa. Tälllöin nähdään onko rokote tehokas.
http://www.aftonbladet.se/nyheter/article16861252.ab
Forskare väldigt nära ett borreliavaccin
Ett fästingbett som lett till borrelia. Foto: Lars Rosengren
Ett borreliavaccin kan bli verklighet om bara några år.
Det unika vaccinet har blivit en stor snackis i forskarvärlden.
– Det ser väldigt lovande ut, säger Rolf Gustafsson, docent i infektionssjukdomar.
Mejla
Fakta
Fästingsjukdomar:
Borrelia är en infektion som orsakas av en grupp bakterier som sprids via fästingar. Fästingen sprider smittan när den suger blod.
Störst risk att få borrelia är i södra och mellersta delarna av Sverige, samt längs landets kuster och insjöar.
Tiden från att man smittats till dess att man får första symptom anges vara från tre dygn upp till en månad.
Cirka 10 000 svenskar får borrelia varje år. Lejonparten får det godartade hudutslaget, men i vissa fall kan infektionen få spridning till centrala nervsystemet, som kan ge hjärnhinneinflamation och förlamning.
Borrelia kan behandlas med antibiotika.
TBE är en annan fästingburen sjukdom som orsakas av ett virus.
Varje år rapporteras 150–200 fall av TBE i Sverige.
Sjukdomen förekommer i södra Sverige. Den är vanligast längs ostkusten och de flesta fallen har smittats inom Upplands och Södermanlands skärgårdar omkring Mälaren.
TBE yttrar sig som en hjärninflammation med hög feber, svår huvudvärk och emellanåt kramper och förlamningar.
Många blir helt återställda men ungefär en tredjedel får långdragna eller bestående besvär med bland annat uttalad trötthet och minnesstörningar.
Källa: Smittskyddsinstitutet, Rolf Gustafsson
Borrelia plågar tusentals svenskar varje år. Än finns inget vaccin mot den plågsamma infektionen som kan resultera i hjärnhinneinflamation och förlamning.
Men nu ser det ut som att forskare är på god väg att besegra den nyckfulla bakterien.
Det är en grupp forskare på det amerikanska läkemedelsföretaget Baxter som har tagit fram vaccinet. Under ett års tid har de jobbat med studien som publicerades i majnumret av den vetenskapliga publikationen The Lancet Infectious Diseases.
Och genombrottet fascinerar forskarvärlden.
Rolf Gustafsson är docent i infektionssjukdomar vid Karolinska institutet och medicinsk chef på Baxter. Han har följt studien som observatör på uppdrag av läkemedelsföretaget.
– Man vet inte hur säkert vaccinet är än. Men man ser att det ser väldigt lovande ut. Nästa fas är att pröva vaccinet i stor skala för att se hur bra det fungerar, säger han.
Unikt vaccin
Rolf Gustafsson beskriver borreliabakterien som väldigt komplicerad. Anledningen är att bakterien byter kläder hela tiden för att vårt immunförsvar inte ska känna igen den. Därför har det varit väldigt svårt för forskare att utveckla ett skydd mot bakterien.
Det finns däremot ett tillstånd då bakterien är helt naken och försvarslös, nämligen när den fortfarande är kvar i fästingen.
Forskarna har därför tagit fram ett vaccin som ska attackera bakterien i just det läget.
– När fästingen kommer till dig för att suga blod så kommer antikropparna som bildats av vaccinet att attackera borreliabakterien som finns i fästingen och se till att den inte överförs till dig. Det är ett slags biologiskt krigföring, säger Rolf Gustafsson.
Konceptet är enligt Gustafsson helt nytt.
– Det är första gången, mig veterligen, som vi har ett vaccin som skyddar utanför människokroppen.
Inga biverkningar
Även Johan Berglund, professor i folkhälsovetenskap på Blekinge Tekniska Högskola och specialist på borrelia, är fascinerad av vaccinet.
– Jag tycker det ser lovande ut. Jag har följt utvecklingen med intresse. Det finns ju ett ganska stort publiktryck från allmänheten för ett borreliavaccin, borrelian är ju så utbredd. Bekymret är att få ett vaccin som täcker alla typer av bakterier. Det har det här kombinationsvaccinet visat sig kunna göra, säger han.
Inga allvarliga biverkningar har hittills rapporterats. Några få symptom forskarna kunnat se är lindrig smärta, svullnad och rodnad.
– Tyvärr kommer man behöva påfyllnadsdoser. Man behöver ta tre doser första året i grundvaccination. Sedan behöver man fylla på kontinuerligt vart tredje år, säger Johan Berglund.
Vaccinet kan vara klart 2018
Hittills har vaccinet bara prövats på 300 personer. År 2015 inleds nästa forskningsfas. Då ska totalt 10 000 personer vaccineras för att se hur effektivt vaccinet är. En testgrupp kommer att finnas i Sverige. Därefter ska data bearbetas och analyseras i ett par år. Trots att utfallet från den större studien kan bli annorlunda är Rolf Gustafsson optimistisk.
– Runt år 2018 kan ett nytt borreliavaccin vara på gång, säger Rolf Gustafsson.
Rokotteen kehittelyn ongelmana on ollut borreliabakteerin kyky muuntua jatkuvasti ja siten estää esim. immuunipuolustusta havaitsemasta sitä. Uusi rokote on kuitenkin kehitetty siten että se suojaa borreliabakteerilta ihmisruumiin ulkopuolella eli rokotteen seurauksena muodostuneet vasta-aineet hyökkäävät bakteeria vastaan siinä vaiheessa kun punkki puree henkilöä eivätkä bakteerit siksi pääse etenemään elimistöön. Rokote perustuu siten aivan uudenlaiseen lähestymistapaan.
Tähän mennessä rokotteen sivuvaikutuksina on ilmennyt lievää kipua, punoitusta ja turvotusta. Rokote saattaa olla valmis vuoteen 2018 mennessä. Rokotteita tarvitaan useita; ensimmäisen vuoden aikana 3 ja sen jälkeen tehostrokote 3 vuoden välein.
Tähän mennessä rokotteen on saanut ainoastaan 300 henkilöä. V. 2015 tutkimusjoukko käsittää 10 000 henkilöä Ruotsissa. Tälllöin nähdään onko rokote tehokas.
http://www.aftonbladet.se/nyheter/article16861252.ab
Forskare väldigt nära ett borreliavaccin
Ett fästingbett som lett till borrelia. Foto: Lars Rosengren
Ett borreliavaccin kan bli verklighet om bara några år.
Det unika vaccinet har blivit en stor snackis i forskarvärlden.
– Det ser väldigt lovande ut, säger Rolf Gustafsson, docent i infektionssjukdomar.
Mejla
Fakta
Fästingsjukdomar:
Borrelia är en infektion som orsakas av en grupp bakterier som sprids via fästingar. Fästingen sprider smittan när den suger blod.
Störst risk att få borrelia är i södra och mellersta delarna av Sverige, samt längs landets kuster och insjöar.
Tiden från att man smittats till dess att man får första symptom anges vara från tre dygn upp till en månad.
Cirka 10 000 svenskar får borrelia varje år. Lejonparten får det godartade hudutslaget, men i vissa fall kan infektionen få spridning till centrala nervsystemet, som kan ge hjärnhinneinflamation och förlamning.
Borrelia kan behandlas med antibiotika.
TBE är en annan fästingburen sjukdom som orsakas av ett virus.
Varje år rapporteras 150–200 fall av TBE i Sverige.
Sjukdomen förekommer i södra Sverige. Den är vanligast längs ostkusten och de flesta fallen har smittats inom Upplands och Södermanlands skärgårdar omkring Mälaren.
TBE yttrar sig som en hjärninflammation med hög feber, svår huvudvärk och emellanåt kramper och förlamningar.
Många blir helt återställda men ungefär en tredjedel får långdragna eller bestående besvär med bland annat uttalad trötthet och minnesstörningar.
Källa: Smittskyddsinstitutet, Rolf Gustafsson
Borrelia plågar tusentals svenskar varje år. Än finns inget vaccin mot den plågsamma infektionen som kan resultera i hjärnhinneinflamation och förlamning.
Men nu ser det ut som att forskare är på god väg att besegra den nyckfulla bakterien.
Det är en grupp forskare på det amerikanska läkemedelsföretaget Baxter som har tagit fram vaccinet. Under ett års tid har de jobbat med studien som publicerades i majnumret av den vetenskapliga publikationen The Lancet Infectious Diseases.
Och genombrottet fascinerar forskarvärlden.
Rolf Gustafsson är docent i infektionssjukdomar vid Karolinska institutet och medicinsk chef på Baxter. Han har följt studien som observatör på uppdrag av läkemedelsföretaget.
– Man vet inte hur säkert vaccinet är än. Men man ser att det ser väldigt lovande ut. Nästa fas är att pröva vaccinet i stor skala för att se hur bra det fungerar, säger han.
Unikt vaccin
Rolf Gustafsson beskriver borreliabakterien som väldigt komplicerad. Anledningen är att bakterien byter kläder hela tiden för att vårt immunförsvar inte ska känna igen den. Därför har det varit väldigt svårt för forskare att utveckla ett skydd mot bakterien.
Det finns däremot ett tillstånd då bakterien är helt naken och försvarslös, nämligen när den fortfarande är kvar i fästingen.
Forskarna har därför tagit fram ett vaccin som ska attackera bakterien i just det läget.
– När fästingen kommer till dig för att suga blod så kommer antikropparna som bildats av vaccinet att attackera borreliabakterien som finns i fästingen och se till att den inte överförs till dig. Det är ett slags biologiskt krigföring, säger Rolf Gustafsson.
Konceptet är enligt Gustafsson helt nytt.
– Det är första gången, mig veterligen, som vi har ett vaccin som skyddar utanför människokroppen.
Inga biverkningar
Även Johan Berglund, professor i folkhälsovetenskap på Blekinge Tekniska Högskola och specialist på borrelia, är fascinerad av vaccinet.
– Jag tycker det ser lovande ut. Jag har följt utvecklingen med intresse. Det finns ju ett ganska stort publiktryck från allmänheten för ett borreliavaccin, borrelian är ju så utbredd. Bekymret är att få ett vaccin som täcker alla typer av bakterier. Det har det här kombinationsvaccinet visat sig kunna göra, säger han.
Inga allvarliga biverkningar har hittills rapporterats. Några få symptom forskarna kunnat se är lindrig smärta, svullnad och rodnad.
– Tyvärr kommer man behöva påfyllnadsdoser. Man behöver ta tre doser första året i grundvaccination. Sedan behöver man fylla på kontinuerligt vart tredje år, säger Johan Berglund.
Vaccinet kan vara klart 2018
Hittills har vaccinet bara prövats på 300 personer. År 2015 inleds nästa forskningsfas. Då ska totalt 10 000 personer vaccineras för att se hur effektivt vaccinet är. En testgrupp kommer att finnas i Sverige. Därefter ska data bearbetas och analyseras i ett par år. Trots att utfallet från den större studien kan bli annorlunda är Rolf Gustafsson optimistisk.
– Runt år 2018 kan ett nytt borreliavaccin vara på gång, säger Rolf Gustafsson.
Re: BORRELIOOSIROKOTE
Aiemmin on ajateltu että borrelioosiin ei kehity lainkaan immuniteettia. Artikkelin mukaan näyttää kuitenkin siltä että mikäli uusi tartunta on aiemmasta, samasta bakteerikannasta, on mahdollista saada vähintään 6v pituinen immuniteetti. Ongelmana on, että useimmiten uusi tartunta on uuden bakteerikannan aiheuttama eikä sitä kohtaan ole muodostunut immuniteettia.
Evidence for strain-specific immunity in patients treated for early Lyme disease
> Camilo E. Khatchikian, Ph.D., Robert B. Nadelman, M.D., John Nowakowski, M.D., Ira Schwartz, Ph.D., Gary P. Wormser, M.D. and Dustin Brisson, Ph.D.
> Infection and Immunity, online before print, January 13, 2014.
>
> http://doi.org/10.1128/IAI.01451-13
>
> Abstract
>
> Lyme disease, caused by Borrelia burgdorferi, is the most commonly reported vector-borne disease in the United States. Many patients treated for early Lyme disease incur another infection in subsequent years, suggesting previous exposure to B. burgdorferi may not elicit a protective immune response.
>
> However, identical strains are almost never detected from patients who are infected multiple times, suggesting that B. burgdorferi exposure may elicit strain specific immunity. Probabilistic and simulation models assuming biologically-realistic data derived from patients in the Northeastern US suggest that patients treated for early Lyme disease develop protective immunity that is strain specific and lasts for at least six years.
>
> http://doi.org/10.1128/IAI.01451-13