Three doses of PCV seem safe and immunogenic in both HIV- and non-HIV-infected children younger than 2 years. This type of vaccine should result in a marked reduction in systemic pneumococcal disease in both HIV- and non-HIV-infected children. Given the high incidence of invasive pneumococcal disease in HIV-infected children, this vaccine may markedly improve the quality of life for this unfortunate group of children.

We conclude that antibody responses to natural infection, PCV and particularly PPV are poorer in HIV-infected than in non-HIV-infected children. PCV is as safe as and more immunogenic than the currently licensed PPV among HIV-infected and non-HIV-infected children.

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The magnitude and duration of vertebrate viremia are critical determinants of arbovirus transmission, geographic spread, and disease severity yet, mechanisms determining arbovirus viremia levels are poorly defined. Previous studies have drawn associations between in vitro virion-glycosaminoglycan (GAG) interactions and in vivo clearance kinetics of virions from blood circulation. From these observations, it is commonly hypothesized that GAG-binding virions are rapidly removed from circulation due to ubiquitous expression of GAGs by vascular endothelial cells, thereby limiting viremia. Using an in vivo model for viremia, we compared the vascular clearance of low and enhanced GAG-binding viral variants of chikungunya (CHIKV), eastern- (EEEV), and Venezuelan- (VEEV) equine encephalitis viruses. We find GAG-binding virions are more quickly removed from circulation than their non-GAG-binding variant; however individual clearance kinetics vary between GAG-binding viruses, from swift (VEEV) to slow removal from circulation (EEEV). Remarkably, we find phagocytes are required for efficient vascular clearance of some enhanced GAG-binding virions. Moreover, transient depletion of vascular heparan sulfate (HS) impedes vascular clearance of only some GAG-binding viral variants and in a phagocyte-dependent manner, implying phagocytes can mediate vascular GAG-virion interactions. Finally, in direct contrast to mice, we find enhanced GAG-binding EEEV is resistant to vascular clearance in avian hosts, suggesting the existence of species-specificity in virion-GAG interactions. In summary, these data support a role for GAG-mediated clearance of some viral particles from the blood circulation, illuminate the potential of blood-contacting phagocytes as a site for GAG-virion binding, and suggest a role for species-specific GAG structures in arbovirus ecology.