The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial

Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Low, Jenny G [verfasserIn] Wijaya, Limin Li, Greg KY Lim, Eleanor YL Shum, Aland KL Cheung, Yin-Bun Ooi, Eng-Eong

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Live vaccination Cross-reactive neutralizing antibodies Innate immune response Adaptive immune response

Anmerkung:	© Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Trials - London : BioMed Central, 2000, 16(2015), 1 vom: 10. Apr.
Übergeordnetes Werk:	volume:16 ; year:2015 ; number:1 ; day:10 ; month:04

Links:	Volltext

DOI / URN:	10.1186/s13063-015-0651-z

Katalog-ID:	SPR030077702

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520			\|a Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013).
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allfields	10.1186/s13063-015-0651-z doi (DE-627)SPR030077702 (SPR)s13063-015-0651-z-e DE-627 ger DE-627 rakwb eng Low, Jenny G verfasserin aut The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). Live vaccination (dpeaa)DE-He213 Cross-reactive neutralizing antibodies (dpeaa)DE-He213 Innate immune response (dpeaa)DE-He213 Adaptive immune response (dpeaa)DE-He213 Wijaya, Limin aut Li, Greg KY aut Lim, Eleanor YL aut Shum, Aland KL aut Cheung, Yin-Bun aut Ooi, Eng-Eong aut Enthalten in Trials London : BioMed Central, 2000 16(2015), 1 vom: 10. Apr. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:16 year:2015 number:1 day:10 month:04 https://dx.doi.org/10.1186/s13063-015-0651-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 10 04
spelling	10.1186/s13063-015-0651-z doi (DE-627)SPR030077702 (SPR)s13063-015-0651-z-e DE-627 ger DE-627 rakwb eng Low, Jenny G verfasserin aut The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). Live vaccination (dpeaa)DE-He213 Cross-reactive neutralizing antibodies (dpeaa)DE-He213 Innate immune response (dpeaa)DE-He213 Adaptive immune response (dpeaa)DE-He213 Wijaya, Limin aut Li, Greg KY aut Lim, Eleanor YL aut Shum, Aland KL aut Cheung, Yin-Bun aut Ooi, Eng-Eong aut Enthalten in Trials London : BioMed Central, 2000 16(2015), 1 vom: 10. Apr. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:16 year:2015 number:1 day:10 month:04 https://dx.doi.org/10.1186/s13063-015-0651-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 10 04
allfields_unstemmed	10.1186/s13063-015-0651-z doi (DE-627)SPR030077702 (SPR)s13063-015-0651-z-e DE-627 ger DE-627 rakwb eng Low, Jenny G verfasserin aut The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). Live vaccination (dpeaa)DE-He213 Cross-reactive neutralizing antibodies (dpeaa)DE-He213 Innate immune response (dpeaa)DE-He213 Adaptive immune response (dpeaa)DE-He213 Wijaya, Limin aut Li, Greg KY aut Lim, Eleanor YL aut Shum, Aland KL aut Cheung, Yin-Bun aut Ooi, Eng-Eong aut Enthalten in Trials London : BioMed Central, 2000 16(2015), 1 vom: 10. Apr. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:16 year:2015 number:1 day:10 month:04 https://dx.doi.org/10.1186/s13063-015-0651-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 10 04
allfieldsGer	10.1186/s13063-015-0651-z doi (DE-627)SPR030077702 (SPR)s13063-015-0651-z-e DE-627 ger DE-627 rakwb eng Low, Jenny G verfasserin aut The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). Live vaccination (dpeaa)DE-He213 Cross-reactive neutralizing antibodies (dpeaa)DE-He213 Innate immune response (dpeaa)DE-He213 Adaptive immune response (dpeaa)DE-He213 Wijaya, Limin aut Li, Greg KY aut Lim, Eleanor YL aut Shum, Aland KL aut Cheung, Yin-Bun aut Ooi, Eng-Eong aut Enthalten in Trials London : BioMed Central, 2000 16(2015), 1 vom: 10. Apr. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:16 year:2015 number:1 day:10 month:04 https://dx.doi.org/10.1186/s13063-015-0651-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 10 04
allfieldsSound	10.1186/s13063-015-0651-z doi (DE-627)SPR030077702 (SPR)s13063-015-0651-z-e DE-627 ger DE-627 rakwb eng Low, Jenny G verfasserin aut The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). Live vaccination (dpeaa)DE-He213 Cross-reactive neutralizing antibodies (dpeaa)DE-He213 Innate immune response (dpeaa)DE-He213 Adaptive immune response (dpeaa)DE-He213 Wijaya, Limin aut Li, Greg KY aut Lim, Eleanor YL aut Shum, Aland KL aut Cheung, Yin-Bun aut Ooi, Eng-Eong aut Enthalten in Trials London : BioMed Central, 2000 16(2015), 1 vom: 10. Apr. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:16 year:2015 number:1 day:10 month:04 https://dx.doi.org/10.1186/s13063-015-0651-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 10 04
language	English
source	Enthalten in Trials 16(2015), 1 vom: 10. Apr. volume:16 year:2015 number:1 day:10 month:04
sourceStr	Enthalten in Trials 16(2015), 1 vom: 10. Apr. volume:16 year:2015 number:1 day:10 month:04
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topic_facet	Live vaccination Cross-reactive neutralizing antibodies Innate immune response Adaptive immune response
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We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. 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topic_title	The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial Live vaccination (dpeaa)DE-He213 Cross-reactive neutralizing antibodies (dpeaa)DE-He213 Innate immune response (dpeaa)DE-He213 Adaptive immune response (dpeaa)DE-He213
topic	misc Live vaccination misc Cross-reactive neutralizing antibodies misc Innate immune response misc Adaptive immune response
topic_unstemmed	misc Live vaccination misc Cross-reactive neutralizing antibodies misc Innate immune response misc Adaptive immune response
topic_browse	misc Live vaccination misc Cross-reactive neutralizing antibodies misc Innate immune response misc Adaptive immune response
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title	The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial
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title_full	The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial
author_sort	Low, Jenny G
journal	Trials
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author_browse	Low, Jenny G Wijaya, Limin Li, Greg KY Lim, Eleanor YL Shum, Aland KL Cheung, Yin-Bun Ooi, Eng-Eong
container_volume	16
format_se	Elektronische Aufsätze
author-letter	Low, Jenny G
doi_str_mv	10.1186/s13063-015-0651-z
title_sort	role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial
title_auth	The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial
abstract	Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. Trial registration Clinical Trials.gov registration number: NCT01943305 (3 September 2013). © Low et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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container_issue	1
title_short	The role of pre-existing cross-reactive antibodies in determining the efficacy of vaccination in humans: study protocol for a randomized controlled trial
url	https://dx.doi.org/10.1186/s13063-015-0651-z
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author2	Wijaya, Limin Li, Greg KY Lim, Eleanor YL Shum, Aland KL Cheung, Yin-Bun Ooi, Eng-Eong
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up_date	2024-07-03T13:46:06.650Z
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