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Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.

Publication ,  Journal Article
Quinnan, GV; Onabajo, O; Zhang, P; Yan, L; Mattapallil, JJ; Zhang, Z; Dong, M; Lu, M; Montefiori, D; LaBranche, C; Broder, CC
Published in: PLoS One
2014

Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02A). Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4), gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L), also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D)) or monomer (gp140-L(M)). Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN) human monoclonal antibodies (mAbs) similarly in ELISA and immunoprecipitation assays. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02A. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction.

Duke Scholars

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

5

Start / End Page

e98060

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Spleen
  • Receptors, CCR5
  • Rabbits
  • Protein Multimerization
  • Protein Binding
  • Neutralization Tests
  • Lymph Nodes
  • Immunization
  • Humans
 

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Quinnan, G. V., Onabajo, O., Zhang, P., Yan, L., Mattapallil, J. J., Zhang, Z., … Broder, C. C. (2014). Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization. PLoS One, 9(5), e98060. https://doi.org/10.1371/journal.pone.0098060
Quinnan, Gerald V., Olusegun Onabajo, Pengfei Zhang, Lianying Yan, Joseph J. Mattapallil, Zhiqiang Zhang, Ming Dong, et al. “Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization.PLoS One 9, no. 5 (2014): e98060. https://doi.org/10.1371/journal.pone.0098060.
Quinnan GV, Onabajo O, Zhang P, Yan L, Mattapallil JJ, Zhang Z, Dong M, Lu M, Montefiori D, LaBranche C, Broder CC. Immunization of rabbits with highly purified, soluble, trimeric human immunodeficiency virus type 1 envelope glycoprotein induces a vigorous B cell response and broadly cross-reactive neutralization. PLoS One. 2014;9(5):e98060.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

5

Start / End Page

e98060

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Spleen
  • Receptors, CCR5
  • Rabbits
  • Protein Multimerization
  • Protein Binding
  • Neutralization Tests
  • Lymph Nodes
  • Immunization
  • Humans