The Centers for Disease Control (CDC) describe vaccinations as among the 10 most significant health achievements ever documented; and for many conditions they have been an unmitigated success (e.g., smallpox). There are, however, several populations in whom vaccine effectiveness is far from optimal. These populations are typically contending with underlying immune impairment by virtue of their advancing age and/or the presence of co-existing diseases (e.g., cancer). As a consequence, vaccines are most likely to fail those whom they most seek to benefit: individuals at the greatest risk of ill health.