Neutralizing Antibodies Protect against Oral Transmission of Lymphocryptovirus

Abstract

SUMMARY Epstein-Barr virus (EBV) is a cancer-associated pathogen for which there is no vaccine. Successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent EBV acquisition. Here we assessed whether passively delivered AMMO1, a monoclonal antibody that neutralizes EBV in a cell-type-independent manner, could protect against experimental EBV challenge in two animal infection models. When present prior to a high-dose intravenous EBV challenge, AMMO1 prevented viremia and reduced viral loads to nearly undetectable levels in humanized mice. AMMO1 conferred sterilizing immunity to three of four macaques challenged orally with rhesus lymphocryptovirus, the EBV ortholog that infects rhesus macaques. The infected macaque had lower plasma neutralizing activity than the protected animals. These results indicate that a vaccine capable of eliciting adequate titers of neutralizing antibodies targeting the AMMO1 epitope may protect against EBV acquisition and are therefore highly relevant to the design of an effective EBV vaccine.

R9AP is a functional receptor for Epstein-Barr virus infection in both epithelial cells and B cells

“…Previous study found that EBV lacking gH failed to infect both epithelial cells and B cells 50 , which indicates the indispensable role of gH in EBV infection. As expected, the human neutralizing antibody AMMO1, which binds to gH/gL D-I to D-II, can block EBV infection of both B cells and epithelial cells 34,35 , but the precise mechanism of neutralization was unknown. These results suggest a potential gH/gL receptor that might be used during EBV infection of epithelial cells and B cells.…”

“…Reagents: Peptides based on amino acids 1 to 50 of R9AP, including R9AP 1-12 (MAREECKALLDG), R9AP [13][14][15][16][17][18][19][20][21][22][23][24] (LNKTTACYHHLV), R9AP [19][20][21][22][23][24][25][26][27][28][29][30] (CYHHLVLTVGGS), R9AP [30][31][32][33][34][35][36][37][38][39][40][41] (SADSQNLRQELQ), and R9AP [35][36][37][38][39][40][41][42][43][44][45][46] (NLRQELQKTRQK), as well as a scrambled control peptide (LVHYTHCGSLGV) were synthesized by CHINESE PEPTIDE (China). The rabbit anti-R9AP antibody used for Western blotting (WB), immuno uorescence staining and immunohistochemistry staining w...…”

“…Reagents: Peptides based on amino acids 1 to 50 of R9AP, including R9AP [1][2][3][4][5][6][7][8][9][10][11][12] (MAREECKALLDG), R9AP [13][14][15][16][17][18][19][20][21][22][23][24] (LNKTTACYHHLV), R9AP [19][20][21][22][23][24][25][26][27][28][29][30] (CYHHLVLTVGGS), R9AP [30][31][32][33][34][35][36][37][38][39][40][41] (SADSQNLRQELQ), and R9AP [35][36][37]…”

“…Several monoclonal antibodies have been identi ed to bind with different domains of gH to block EBV infection in either B cells or epithelial cells. However, AMMO1 is so far the only reported monoclonal antibody that binds gH/gL and blocks not only EBV infection of both epithelial cells and B cells in vitro but also EBV infection in animal infection models 34,35 . AMMO1 interacts with a discontinuous epitope among gH/gL D-I and D-II, but its precise mechanism of neutralization is unknown.…”

Association between Antibody Responses to Epstein-Barr Virus Glycoproteins, Neutralization of Infectivity, and the Risk of Nasopharyngeal Carcinoma

“…And in the humanized mouse model, AMMO1 showed excellent neutralizing ability against EBV infection of lymphocyte populations. However, 72A1, which was thought to be a neutralizing antibody targeting gp350, failed to prevent EBV-driven changes and reduce the viral load in humanized mice ( 26 ). Bu et al found that antibodies to EBV gH/gL play an important role in epithelial-cell and B-cell-neutralizing titers against EBV infection in human plasma ( 16 ).…”