scholarly journals Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice

2015 ◽  
Vol 26 (9) ◽  
pp. 622-634 ◽  
Author(s):  
Shan Liu ◽  
Andrew Jackson ◽  
Jagadish Beloor ◽  
Priti Kumar ◽  
Richard E. Sutton
2008 ◽  
Vol 72 (1) ◽  
pp. 54-84 ◽  
Author(s):  
Marinieve Montero ◽  
Nienke E. van Houten ◽  
Xin Wang ◽  
Jamie K. Scott

SUMMARY Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented.


2007 ◽  
Vol 81 (16) ◽  
pp. 8533-8542 ◽  
Author(s):  
Esther D. Quakkelaar ◽  
Floris P. J. van Alphen ◽  
Brigitte D. M. Boeser-Nunnink ◽  
Ad C. van Nuenen ◽  
Ralph Pantophlet ◽  
...  

ABSTRACT The ability of the broadly neutralizing human immunodeficiency virus type 1 (HIV-1) specific human monoclonal antibodies (MAbs) b12, 2G12, 2F5, and 4E10 to neutralize recently transmitted viruses has not yet been explored in detail. We investigated the neutralization sensitivity of subtype B HIV-1 variants obtained from four primary HIV infection cases and six transmission couples (four homosexual and two parenteral) to these MAbs. Sexually transmitted HIV-1 variants isolated within the first 2 months after seroconversion were generally sensitive to 2F5, moderately resistant to 4E10 and b12, and initially resistant but later more sensitive to 2G12 neutralization. In the four homosexual transmission couples, MAb neutralization sensitivity of HIV in recipients did not correlate with the MAb neutralization sensitivity of HIV from their source partners, whereas the neutralization sensitivity of donor and recipient viruses involved in parenteral transmission was more similar. For a fraction (11%) of the HIV-1 variants analyzed here, neutralization by 2G12 could not be predicted by the presence of N-linked glycosylation sites previously described to be involved in 2G12 binding. Resistance to 2F5 and 4E10 neutralization did also not correlate with mutations in the respective core epitopes. Overall, we observed that the neutralization resistance of recently transmitted subtype B HIV-1 variants was relatively high. Although 8 of 10 patients had viruses that were sensitive to neutralization by at least one of the four broadly neutralizing antibodies studied, 4 of 10 patients harbored at least one virus variant that seemed resistant to all four antibodies. Our results suggest that vaccine antigens that only elicit antibodies equivalent to b12, 2G12, 2F5, and 4E10 may not be sufficient to protect against all contemporary HIV-1 variants and that additional cross-neutralizing specificities need to be sought.


Virology ◽  
2007 ◽  
Vol 363 (2) ◽  
pp. 447-453 ◽  
Author(s):  
Esther D. Quakkelaar ◽  
Evelien M. Bunnik ◽  
Floris P.J. van Alphen ◽  
Brigitte D.M. Boeser-Nunnink ◽  
Ad C. van Nuenen ◽  
...  

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