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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

Sequentially elicited antibodies to HIV-1 envelope over the course of the infection.
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Figure 1: Sequentially elicited antibodies to HIV-1 envelope over the course of the infection.

Mentions: The first detectable antibodies directed against the HIV-1 envelope appear around 12 days after infection. These antibodies are non-neutralizing, directed against the gp41 region, and mainly forming immune complexes (Tomaras and Haynes, 2009; Figure 1). Approximately 2 weeks later, antibodies are formed against the immunodominant gp120 region and these are also non-neutralizing. Neutralizing antibodies appear for the first time around 3 months post-seroconversion. These antibodies are mostly strain-specific and cannot neutralize heterologous viruses. Autologous neutralizing antibodies can rapidly select for escape variants of HIV-1 and do not seem to have a protective effect against progression to AIDS (Richman et al., 2003; Wei et al., 2003; Bunnik et al., 2008; Mahalanabis et al., 2009; van Gils et al., 2010). HIV-1 envelope is one of the most extensively glycosylated proteins found in nature (Myers and Lenroot, 1992). The glycans on the protein shield the conserved envelope domains from recognition by neutralizing antibodies. Also, as the glycans originate from the host cell machinery, they are usually not recognized by the immune system as foreign. Removal of glycosylation sites within or around the variable domains made the virus more susceptible to antibody neutralization (Reitter et al., 1998; Binley et al., 2010). The virus can escape neutralizing antibodies through additional potential N-linked glycosylation sites (PNGS) in the viral envelope or through changed positions of PNGS. The envelope also contains hypervariable regions that can change in length or amino acid sequence. HIV-1 variants with these changes can be rapidly selected under neutralizing antibody pressure if these changes coincide with an increased resistance to circulating neutralizing antibodies. Broadly neutralizing antibodies are directed against conserved regions of the virus and therefore capable of neutralizing a large variety of viruses from different subtypes. As these broadly neutralizing antibodies generally neutralize the majority of recently transmitted HIV-1 variants (Binley et al., 2004; Bunnik et al., 2010; Euler et al., 2011), irrespective of number of PNGS and variable loop length, a vaccine should be able to elicit this type of antibodies.


Cross-reactive broadly neutralizing antibodies: timing is everything.

Euler Z, Schuitemaker H - Front Immunol (2012)

Sequentially elicited antibodies to HIV-1 envelope over the course of the infection.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Sequentially elicited antibodies to HIV-1 envelope over the course of the infection.
Mentions: The first detectable antibodies directed against the HIV-1 envelope appear around 12 days after infection. These antibodies are non-neutralizing, directed against the gp41 region, and mainly forming immune complexes (Tomaras and Haynes, 2009; Figure 1). Approximately 2 weeks later, antibodies are formed against the immunodominant gp120 region and these are also non-neutralizing. Neutralizing antibodies appear for the first time around 3 months post-seroconversion. These antibodies are mostly strain-specific and cannot neutralize heterologous viruses. Autologous neutralizing antibodies can rapidly select for escape variants of HIV-1 and do not seem to have a protective effect against progression to AIDS (Richman et al., 2003; Wei et al., 2003; Bunnik et al., 2008; Mahalanabis et al., 2009; van Gils et al., 2010). HIV-1 envelope is one of the most extensively glycosylated proteins found in nature (Myers and Lenroot, 1992). The glycans on the protein shield the conserved envelope domains from recognition by neutralizing antibodies. Also, as the glycans originate from the host cell machinery, they are usually not recognized by the immune system as foreign. Removal of glycosylation sites within or around the variable domains made the virus more susceptible to antibody neutralization (Reitter et al., 1998; Binley et al., 2010). The virus can escape neutralizing antibodies through additional potential N-linked glycosylation sites (PNGS) in the viral envelope or through changed positions of PNGS. The envelope also contains hypervariable regions that can change in length or amino acid sequence. HIV-1 variants with these changes can be rapidly selected under neutralizing antibody pressure if these changes coincide with an increased resistance to circulating neutralizing antibodies. Broadly neutralizing antibodies are directed against conserved regions of the virus and therefore capable of neutralizing a large variety of viruses from different subtypes. As these broadly neutralizing antibodies generally neutralize the majority of recently transmitted HIV-1 variants (Binley et al., 2004; Bunnik et al., 2010; Euler et al., 2011), irrespective of number of PNGS and variable loop length, a vaccine should be able to elicit this type of antibodies.

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