Novel Vaccines for the Older Adult

Currently, we still lack vaccines against many pathogens that are of particular relevance for the old, despite substantial effort put into their development. Respiratory syncytial virus (RSV) is a major cause of severe respiratory infection in infants. For adults, RSV infection is usually associated with only mild or moderate symptoms. However, persons with underlying chronic diseases and frail older adults are susceptible to severe disease. It has been estimated that almost 18,000 hospitalizations and 8400 deaths caused by RSV occur in the United Kingdom per season and that 79 % of the hospitalizations and 93 % of deaths were in persons older than 65 years. High-risk elderly (with chronic conditions such as COPD, cardiovascular disease, renal and liver disorders, immunosuppressive therapy etc.) have an increased rate of hospitalization (fourfold) and death (twofold) compared to low-risk older patients [106]. A first paediatric vaccine candidate against RSV has been developed in the 1960s, but was associated with a risk of enhanced disease in vaccinated children [107]. This failure hampered vaccine development for a long time, but nowadays several novel vaccine candidates against RSV are in clinical development, including vaccines based on recombinant proteins, virus-like particles and live-attenuated vaccines [108]. It will be of utmost importance that these vaccine candidates will be further developed not only for the paediatric market, but also tested in adults and the old.

Vaccines against nosocomial infections are highly desirable, particularly as antibiotic resistance is increasing for many bacterial species. Nevertheless, no such vaccine is currently licensed. The risk of nosocomial infections is particularly high for the old, as they are more often hospitalized, are at higher risk of invasive procedures (surgery, prostheses, catheters etc.) and are more susceptible to severe consequences and death in case of infection. Staphylococcus aureus infections range from mild skin infections to potentially fatal pneumonia and invasive disease [109]. Two vaccine candidates targeting single antigens have been clinically tested [110, 111], but had only limited or no efficacy against S. aureus infection. Three next- generation vaccines comprising several antigens are currently in early clinical development [112]. Most cases of nosocomial infectious diarrhea are caused by Clostridium difficile [113] and 81 % of cases in England have been reported to occur in older persons, in whom mortality is also increased [114]. Highly virulent strains have emerged and become endemic in hospitals, and antibiotic resistance is a growing problem. Clinical symptoms are caused by bacterial toxins and therefore vaccination strategies aim to elicit toxin-neutralizing antibodies. Clinical development is ongoing for three toxin-based vaccines and first results indicate the induction of neutralizing antibodies in healthy adults including older individuals [112]. Vaccines against these two and other nosocomial pathogens, such as Escherichia coli, Klebsiella pneumoniae and Candida ssp. [115] have the potential to save many lives and to substantially reduce healthcare costs.

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