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Cross-reactive broadly neutralizing antibodies: timing is everything.

Euler Z, Schuitemaker H - Front Immunol (2012)

Bottom Line: The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology.In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection.We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

View Article: PubMed Central - PubMed

Affiliation: Landsteiner Laboratory, Sanquin Research, Amsterdam, Netherlands.

ABSTRACT
The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology. In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection. We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

No MeSH data available.


Related in: MedlinePlus

Epitope specificity of known broadly neutralizing antibodies to HIV-1 envelope. Adapted from White et al. (2010).
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Figure 2: Epitope specificity of known broadly neutralizing antibodies to HIV-1 envelope. Adapted from White et al. (2010).

Mentions: Prior to 2009, the presence of broadly neutralizing antibodies in HIV-1-infected individuals was considered rare. At that time, only four monoclonal antibodies (MAbs) had been isolated that could potently neutralize a majority of primary HIV-1 strains (Figure 2). MAb b12 was the first broadly neutralizing antibody and obtained from the bone marrow of an asymptomatic HIV-infected man (Burton et al., 1994; Kessler et al., 1997; Saphire et al., 2001). More specifically, it was isolated from a phage display library in which heavy and light chains are recombined in vitro to Fab fragments, and subsequently modified into complete IgG molecules. This may imply that the b12 antibody had not existed in vivo in the patient but only emerged due to in vitro recombination of heavy and light chains. The epitope on HIV-1 that is recognized by b12 lies in the CD4-binding site of the envelope. Crystal structures have revealed that the contact surfaces of b12 and CD4 on the viral envelope are considerably overlapping (Zhou et al., 2007), which could explain the neutralizing activity. However, overlap with the CD4-binding site alone is not sufficient for neutralization as the footprint for b12 on the CD4-binding site in Env overlaps with the footprints of antibodies b3 and b6 which are highly related to b12 but non-neutralizing. Antibodies b3 and b6 bind beyond the neutralizing face, into the non-neutralizing face and are unlike b12, not able to bind to trimeric Env (Pantophlet et al., 2003).


Cross-reactive broadly neutralizing antibodies: timing is everything.

Euler Z, Schuitemaker H - Front Immunol (2012)

Epitope specificity of known broadly neutralizing antibodies to HIV-1 envelope. Adapted from White et al. (2010).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3400945&req=5

Figure 2: Epitope specificity of known broadly neutralizing antibodies to HIV-1 envelope. Adapted from White et al. (2010).
Mentions: Prior to 2009, the presence of broadly neutralizing antibodies in HIV-1-infected individuals was considered rare. At that time, only four monoclonal antibodies (MAbs) had been isolated that could potently neutralize a majority of primary HIV-1 strains (Figure 2). MAb b12 was the first broadly neutralizing antibody and obtained from the bone marrow of an asymptomatic HIV-infected man (Burton et al., 1994; Kessler et al., 1997; Saphire et al., 2001). More specifically, it was isolated from a phage display library in which heavy and light chains are recombined in vitro to Fab fragments, and subsequently modified into complete IgG molecules. This may imply that the b12 antibody had not existed in vivo in the patient but only emerged due to in vitro recombination of heavy and light chains. The epitope on HIV-1 that is recognized by b12 lies in the CD4-binding site of the envelope. Crystal structures have revealed that the contact surfaces of b12 and CD4 on the viral envelope are considerably overlapping (Zhou et al., 2007), which could explain the neutralizing activity. However, overlap with the CD4-binding site alone is not sufficient for neutralization as the footprint for b12 on the CD4-binding site in Env overlaps with the footprints of antibodies b3 and b6 which are highly related to b12 but non-neutralizing. Antibodies b3 and b6 bind beyond the neutralizing face, into the non-neutralizing face and are unlike b12, not able to bind to trimeric Env (Pantophlet et al., 2003).

Bottom Line: The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology.In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection.We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

View Article: PubMed Central - PubMed

Affiliation: Landsteiner Laboratory, Sanquin Research, Amsterdam, Netherlands.

ABSTRACT
The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology. In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection. We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

No MeSH data available.


Related in: MedlinePlus