Humoral Immune Responses to HIV-1: Fighting Evolution with Evolution

Among the most pressing global public health problems at present is the AIDS epidemic.  While it is clear that chemotherapy and behavioral interventions have much to offer in limiting the spread of infections by the causative virus, HIV-1, interest in developing a vaccine remains strong.  Immunization would potentially provide a relatively cost-effective and scalable approach to minimizing the incidence of new infections on a global scale.

However, HIV-1 presents numerous challenges to would-be vaccine developers.  There are many different lineages of HIV-1 viruses with different clades dominating in different geographic regions of the world.  Even in a single infected patient, HIV-1 continues to generate many variants.  Astonishingly, according to Korber et al. (2001), “The diversity of influenza sequences world-wide in any given year appears to be roughly comparable to the diversity of HIV sequences found within a single infected individual at one time point ….  The virion surface protein, gp120, which is critically involved in infecting host cells and is a major target for protective antibodies, contains regions that are especially variable in amino acid sequence.

In addition to the serious challenge of eliciting an immune response, of whatever sort, that can effectively provide immunity to the many viral variants in circulation, it remains unclear what types of immune responses are essential for providing a high level of protection against infection or disease.  Some investigators are focsed on eliciting strong cell-mediated immune response.  Others are devoting their efforts to generating humoral responses including potent and broadly-neutralizing antibodies.  There are several recent and interesting reports pertaining to this latter effort. (more…)

A Genomic Perspective on Pathogen Adaptation to Antibiotics and Vaccines

Among human pathogens, Streptococcus pneumoniae holds an especially prominent place in the history of biomedical investigation.  Griffith (1928) described the transforming principle, a soluble substance released by dead, virulent pneumococci that could render living avirulent pneumococci able to effectively kill a mouse.  Oswald Avery’s commitment to curing pneumococcal pneumonia (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/37) led him and his collaborators to determine that the pneumococcal transforming principle was DNA (Avery et al., 1944).  It was also Avery’s and his collaborators’ work on pneumococci that provided some of the first insights into the chemical nature of most bacterial capsules. (more…)

Evolutionary Origins of a Potent Broadly-Neutralizing Antibody to HIV-1

Two recent papers published online at scienceexpress.org describe studies of antibodies claimed to interfere with infection of host cells by a wide range of HIV-1 strains.  These studies strongly suggest that the evolutionary potential of the humoral immune response may be necessary to combat the diversity of HIV-1 antigens that results from the extraordinary pace of HIV-1 evolution. (more…)

Phenotypic noise and the evolution of virulence

Commentary on: M. Ackermann, B. Stecher, N. E. Freed, P. Songhet, W.-D. Hardt, and M. Doebeli (2008) Self-destructive cooperation mediated by phenotype noise. Nature 454:987-9

One of the most exciting developments in microbial population biology over the past few years is the recognition that high levels of phenotypic noise – in which genetically identical microbes express different genes and manifest different phenotypes despite a common environment – is widespread in bacterial populations and that this noise plays an important role in bacterial evolutionary ecology (e.g. Elowitz et al. 2002, Balaban et al. 2004, Rosenfeld et al. 2005, Acar et al. 2008, Veening et al. 2008). I have always thought that the best explanations for this phenomenon involve bet hedging in uncertain environments (Seger and Brockmann 1987), and indeed this bet-hedging perspective has been well supported by mathematical modeling (e.g. Thattai and van Oudenaarden 2004, Kussell et al. 2005).

But in this week’s issue of Nature, Martin Ackermann and colleagues propose an alternative explanation (more…)