TY - JOUR
T1 - Two-component vaccine consisting of virus-like particles displaying hepatitis C virus envelope protein 2 oligomers
AU - Prentoe, Jannick
AU - Janitzek, Christoph M
AU - Velázquez-Moctezuma, Rodrigo
AU - Soerensen, Andreas
AU - Jørgensen, Thomas
AU - Clemmensen, Stine
AU - Soroka, Vladislav
AU - Thrane, Susan
AU - Theander, Thor
AU - Nielsen, Morten A
AU - Salanti, Ali
AU - Bukh, Jens
AU - Sander, Adam F
N1 - © 2022. The Author(s).
PY - 2022/11/15
Y1 - 2022/11/15
N2 - Development of B-cell-based hepatitis C virus (HCV) vaccines that induce broadly neutralizing antibodies (bNAbs) is hindered by extensive sequence diversity and low immunogenicity of envelope glycoprotein vaccine candidates, most notably soluble E2 (sE2). To overcome this, we employed two-component approaches using self-assembling virus-like particles (cVLPs; component 1), displaying monomeric or oligomeric forms of HCV sE2 (sE2mono or sE2oligo; component 2). Immunization studies were performed in BALB/c mice and the neutralizing capacity of vaccine-induced antibodies was tested in cultured-virus-neutralizations, using HCV of genotypes 1-6. sE2-cVLP vaccines induced significantly higher levels of NAbs (p = 0.0065) compared to corresponding sE2 vaccines. Additionally, sE2oligo-cVLP was superior to sE2mono-cVLP in inducing bNAbs. Interestingly, human monoclonal antibody AR2A had reduced binding in ELISA to sE2oligo-cVLP compared with sE2mono-cVLP and competition ELISA using mouse sera from vaccinated animals indicated that sE2oligo-cVLP induced significantly less non-bNAbs AR2A (p = 0.0043) and AR1B (p = 0.017). Thus, cVLP-displayed oligomeric sE2 shows promise as an HCV vaccine candidate.
AB - Development of B-cell-based hepatitis C virus (HCV) vaccines that induce broadly neutralizing antibodies (bNAbs) is hindered by extensive sequence diversity and low immunogenicity of envelope glycoprotein vaccine candidates, most notably soluble E2 (sE2). To overcome this, we employed two-component approaches using self-assembling virus-like particles (cVLPs; component 1), displaying monomeric or oligomeric forms of HCV sE2 (sE2mono or sE2oligo; component 2). Immunization studies were performed in BALB/c mice and the neutralizing capacity of vaccine-induced antibodies was tested in cultured-virus-neutralizations, using HCV of genotypes 1-6. sE2-cVLP vaccines induced significantly higher levels of NAbs (p = 0.0065) compared to corresponding sE2 vaccines. Additionally, sE2oligo-cVLP was superior to sE2mono-cVLP in inducing bNAbs. Interestingly, human monoclonal antibody AR2A had reduced binding in ELISA to sE2oligo-cVLP compared with sE2mono-cVLP and competition ELISA using mouse sera from vaccinated animals indicated that sE2oligo-cVLP induced significantly less non-bNAbs AR2A (p = 0.0043) and AR1B (p = 0.017). Thus, cVLP-displayed oligomeric sE2 shows promise as an HCV vaccine candidate.
UR - http://www.scopus.com/inward/record.url?scp=85141835911&partnerID=8YFLogxK
U2 - 10.1038/s41541-022-00570-1
DO - 10.1038/s41541-022-00570-1
M3 - Journal article
C2 - 36379958
SN - 2059-0105
VL - 7
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 148
ER -