TY - JOUR
T1 - Effects of GP120 inner domain (ID2) immunogen doses on elicitation of anti-HIV-1 functional FC-effector response to C1/C2 (cluster a) epitopes in mice
AU - Sherburn, Rebekah
AU - Tolbert, William D.
AU - Gottumukkala, Suneetha
AU - Beaudoin-Bussières, Guillaume
AU - Finzi, Andrés
AU - Pazgier, Marzena
N1 - Funding Information:
Funding: Funding for this study was provided by the National Institute of Health grants R01 AI116274 to M.P. and R01 AI129769 to M.P. and A.F., and P01 AI120756 to Georgia Tomaras. This work was also supported by a CIHR foundation grant #352417 to A.F. A.F. is the recipient of a Canada Research Chair on Retroviral Entry # RCHS0235 950-232424. G.B.-B. is supported by a CIHR fellowship. Funding bodies had no role in the design, collection, analysis or interpretation of the data. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript and the contents of this publication are solely the responsibility of the authors.
Funding Information:
for this study was provided by the National Institute of Health grants R01 AI116274 to M.P. and R01 AI129769 to M.P. and A.F., and P01 AI120756 to Georgia Tomaras. This work was also supported by a CIHR foundation grant #352417 to A.F. A.F. is the recipient of a Canada Research Chair on Retroviral Entry # RCHS0235 950-232424. G.B.-B. is supported by a CIHR fellowship. Funding bodies had no role in the design, collection, analysis or interpretation of the data. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript and the contents of this publication are solely the responsibility of the authors. Acknowledgments: We thank George Lewis of the University of Maryland for providing the cell line for RFADCC assays.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10
Y1 - 2020/10
N2 - Fc-mediated effector functions of antibodies, including antibody-dependent cytotoxicity (ADCC), have been shown to contribute to vaccine-induced protection from HIV-1 infection, especially those directed against non-neutralizing, CD4 inducible (CD4i) epitopes within the gp120 constant 1 and 2 regions (C1/C2 or Cluster A epitopes). However, recent passive immunization studies have not been able to definitively confirm roles for these antibodies in HIV-1 prevention mostly due to the complications of cross-species Fc–FcR interactions and suboptimal dosing strategies. Here, we use our stabilized gp120 Inner domain (ID2) immunogen that displays the Cluster A epitopes within a minimal structural unit of HIV-1 Env to investigate an immunization protocol that induces a fine-tuned antibody repertoire capable of an effective Fc-effector response. This includes the generation of isotypes and the enhanced antibody specificity known to be vital for maximal Fc-effector activities, while minimizing the induction of isotypes know to be detrimental for these functions. Although our studies were done in in BALB/c mice we conclude that when optimally titrated for the species of interest, ID2 with GLA-SE adjuvant will elicit high titers of antibodies targeting the Cluster A region with potent Fc-mediated effector functions, making it a valuable immunogen candidate for testing an exclusive role of non-neutralizing antibody response in HIV-1 protection in vaccine settings.
AB - Fc-mediated effector functions of antibodies, including antibody-dependent cytotoxicity (ADCC), have been shown to contribute to vaccine-induced protection from HIV-1 infection, especially those directed against non-neutralizing, CD4 inducible (CD4i) epitopes within the gp120 constant 1 and 2 regions (C1/C2 or Cluster A epitopes). However, recent passive immunization studies have not been able to definitively confirm roles for these antibodies in HIV-1 prevention mostly due to the complications of cross-species Fc–FcR interactions and suboptimal dosing strategies. Here, we use our stabilized gp120 Inner domain (ID2) immunogen that displays the Cluster A epitopes within a minimal structural unit of HIV-1 Env to investigate an immunization protocol that induces a fine-tuned antibody repertoire capable of an effective Fc-effector response. This includes the generation of isotypes and the enhanced antibody specificity known to be vital for maximal Fc-effector activities, while minimizing the induction of isotypes know to be detrimental for these functions. Although our studies were done in in BALB/c mice we conclude that when optimally titrated for the species of interest, ID2 with GLA-SE adjuvant will elicit high titers of antibodies targeting the Cluster A region with potent Fc-mediated effector functions, making it a valuable immunogen candidate for testing an exclusive role of non-neutralizing antibody response in HIV-1 protection in vaccine settings.
KW - ADCC
KW - Dosing
KW - Fc-mediated effector functions
KW - HIV-1
KW - Inner domain (ID2) immunogen
KW - Isotype
KW - Non-neutralizing antibody response
UR - http://www.scopus.com/inward/record.url?scp=85091717431&partnerID=8YFLogxK
U2 - 10.3390/microorganisms8101490
DO - 10.3390/microorganisms8101490
M3 - Article
AN - SCOPUS:85091717431
SN - 2076-2607
VL - 8
SP - 1
EP - 17
JO - Microorganisms
JF - Microorganisms
IS - 10
M1 - 1490
ER -