Biology Reference
In-Depth Information
protomers appear to fold over gp41 rather than depart radially from
it, contacting each other at the top of the spike. The interaction
between gp120 monomers at this contact is likely to be weak, to allow
the disassembly of Env ectodomain and extrusion of gp41 for inser-
tion into the host membrane for the membrane fusion to take place.
The two models proposed shed light on several important anti-
genic and mechanistic features of the Env trimer. First, they provide
models consistent with the concept that glycans and immunodomi-
nant variable loops are positioned on exposed gp120 surfaces to damp
the neutralizing antibody response. Second, they confirm that only a
limited gp41 surface is exposed for antibody binding, as has been pro-
posed previously.
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Third, they provide two possible descriptions of
the position of the V3 loop and the co-receptor binding.
B.
Approaches to Overcome Genetic Diversity of
HIV Env for Vaccine Development
HIV is one of the most genetically diverse viral pathogens studied to
date. The uneven distribution of the various clades across the globe
presents one of the most challenging aspects to HIV vaccine design,
as it is unknown whether it will be possible to make an HIV vaccine
to cover all clades or whether a tailor-made vaccine based on the most
prevalent strain for a given region will be needed. To address the
problem of genetic diversity in HIV multivalent vaccine formulations
and vaccines based on consensus and ancestral sequences are being
evaluated.
Multivalent vaccine approach
The objective of this approach is to use multiple clade-specific
immunogens in a vaccine to increase the breadth of the immune
responses without compromising the potency against one or more
clades. Various groups have recently demonstrated the potential util-
ity of this approach. For example, Shan Lu and colleagues demon-
strated that by including monomeric Envs from different clades,
improved breadth of neutralizing antibodies against different subtypes
