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An improved conjugate vaccine technology; induction of antibody responses to the tumor vasculature

HUIJBERS, Elisabeth J M, et al.

Abstract

The induction of an antibody response against self-antigens requires a conjugate vaccine technology, where the self-antigen is conjugated to a foreign protein sequence, and the co-application of a potent adjuvant. The choice of this foreign sequence is crucial as a very strong antibody response towards it may compromise the anti-self immune response. Here, we aimed to optimize the conjugate design for application of vaccination against the tumor vasculature, using two different approaches. First, the immunogenicity of the previously employed bacterial thioredoxin (TRX) was reduced by using a truncated from (TRXtr).

Second, the Escherichia coli proteome was scrutinized to identify alternative proteins, based on immunogenicity and potency to increase solubility, suitable for use in a conjugate vaccine.

This technology was used for vaccination against a marker of the tumor vasculature, the well-known extra domain B (EDB) of fibronectin. We demonstrate that engineering of the foreign sequence of a conjugate vaccine can significantly improve antibody production. The TRXtr construct outperformed the one containing full-length [...]

HUIJBERS, Elisabeth J M, et al . An improved conjugate vaccine technology; induction of antibody responses to the tumor vasculature. Vaccine , 2018, vol. 36, no. 21, p. 3054-3060

DOI : 10.1016/j.vaccine.2018.03.064 PMID : 29655625

Available at:

http://archive-ouverte.unige.ch/unige:138154

Disclaimer: layout of this document may differ from the published version.

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Corrigendum

Corrigendum to ‘‘An improved conjugate vaccine technology;

induction of antibody responses to the tumor vasculature”

[Vaccine 36(21) 3054–3060]

Elisabeth J.M. Huijbers

a

, Judy R. van Beijnum

a

, Chung T. Lê

a

, Sophia Langman

a

, Patrycja Nowak-Sliwinska

b

, Kevin H. Mayo

c

, Arjan W. Griffioen

a,

aAngiogenesis Laboratory, Cancer Center Amsterdam, Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands

bSchool of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland

cDepartment of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN, USA

The authors of Huijbers et al.[1]apologize for not giving suffi- cient credit to the work presented by Saupe et al.[2], Huijbers et al.

[3]and Femel et al.[4]. Below are corrections to the relevant parts of the article. The authors would like to apologize for any inconve- nience caused.

Page 3054 (Introduction)

The sentence: ‘In previous work we have shown that it is possi- ble to break self-tolerance in mice, and to induce antibody responses against the tumor vascular markers extra domain A (EDA) and B (EDB) of the extracellular matrix molecule fibronectin.’,

should be replaced by:

‘Previous work of Huijbers et al. [3] and Femel et al. [4]has shown that it is possible to break self-tolerance in mice, and to induce antibody responses against the tumor vascular markers extra domain A (EDA) and B (EDB) of the extracellular matrix mole- cule fibronectin.’

Page 3056 (Discussion)

The sentence: ‘We have previously shown that the anti-self antibody response against EDB is decreased as the amount of TRX is increased.’,

should be replaced by:

‘Saupe et al.[2]have previously shown that the anti-self anti- body response against EDB is decreased as the amount of TRX is increased.’

Page 3057 (Discussion)

The sentence: ‘In this paper we show that the TRX-part is abso- lutely required to induce an immune response against EDB and that vaccination with EDB alone does not induce an antibody response against EDB.’,

should be replaced by:

‘In this paper Saupe et al.[2]show that the TRX-part is abso- lutely required to induce an immune response against EDB and

that vaccination with EDB alone does not induce an antibody response against EDB.’

Page 3058 (Discussion)

The sentence: ‘To address this issue, we have previously used the MMTV-PyMT transgenic model of breast cancer. Since EDB is not expressed in this model we approached the question with a vaccine against the extra domain A of fibronectin (EDA).’,

should be replaced by:

‘This issue was previously addressed by Femel et al.[4]using the MMTV-PyMT transgenic model of breast cancer. Since EDB is not expressed in this model the question was approached with a vaccine against the extra domain A of fibronectin (EDA).’

The sentence: ‘We have looked into more detail at the immune response induced with the TRX-EDB vaccine [12] and found that the major subclass induced by the vaccine was IgG1, which is char- acteristic of a Th2-response, thus an antibody mediated immune response in mice. Furthermore, we found macrophages trying to engulf the tumor vessels in the tumors of mice vaccinated with TRX-EDB, increased fibrinogen leakage and increased neutrophil infiltration in these tumors.’,

should be replaced by:

‘Huijbers et al.[3]have looked into more detail at the immune response induced with the TRX-EDB vaccine and found that the major subclass induced by the vaccine was IgG1, which is charac- teristic of a Th2-response, thus an antibody mediated immune response in mice. Furthermore, they found macrophages trying to engulf the tumor vessels in the tumors of mice vaccinated with TRX-EDB, increased fibrinogen leakage and increased neutrophil infiltration in these tumors.’

After the sentence: ‘The current study demonstrates that sev- eral alternative non-self fusion partners in conjugate vaccines can elicit strong and specific antibody responses against self- antigens.’,

this sentence should be added:

‘This was also observed in a study by Saupe et al. in which VLRB (variable lymphocyte receptor B) conjugate vaccines were used[2].

This study concluded that the foreign antigen should be short

https://doi.org/10.1016/j.vaccine.2019.06.010

0264-410X/Ó2019 The Author(s). Published by Elsevier Ltd.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of original article:https://doi.org/10.1016/j.vaccine.2018.03.064

Corresponding author.

E-mail address:aw.griffioen@vumc.nl(A.W. Griffioen).

Vaccine 37 (2019) 4231–4232

Contents lists available atScienceDirect

Vaccine

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / v a c c i n e

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(around 41 aa in size), have multimerizing capacity to provide a strong B cell activation signal and be hidden inside the vaccine protein to avoid epitope masking or clearance of the fusion protein.’

Page 3058 (Experimental procedures)

The sentence: ‘The pET21-TRX vector was a kind gift of Dr. Anna-Karin Olsson (Uppsala University, Uppsala, Sweden).’,

should be replaced by:

‘Both the pET21-TRX vector and the pET21a-TRX-EDB vector were a kind gift of Dr. Anna-Karin Olsson (Uppsala University, Uppsala, Sweden).’

References

[1]Huijbers EJM, Van Beijnum JR, Le CT, Langman S, Patrycja Nowak-Sliwinska P, Mayo KH, et al. An improved conjugate vaccine technology; induction of antibody responses to the tumor vasculature. Vaccine 2018;36:3054–60.

[2]Saupe F, Reichel M, Huijbers EJ, Femel J, Markgren PO, Andersson CE, et al.

Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously. FASEB J 2017;31:1204–14.

[3]Huijbers EJ, Ringvall M, Femel J, Kalamajski S, Lukinius A, Abrink M, et al.

Vaccination against the extra domain-B of fibronectin as a novel tumor therapy.

Faseb J 2010;24:4535–44.

[4]Femel J, Huijbers EJ, Saupe F, Cedervall J, Zhang L, Roswall P, et al. Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer. Oncotarget 2014;5:12418–27.

4232 E.J.M. Huijbers et al. / Vaccine 37 (2019) 4231–4232

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