New Developments in Adult Vaccination: Challenges and Opportunities to Protect Vulnerable Veterans From Pneumococcal Disease

Streptococcus pneumoniae (S pneumoniae), also known as pneumococcus, is a successful human pathogen with significant clinical impact that causes pneumonia and invasive infections, including bacteremia and meningitis.¹ In the preantibiotic era, nearly 80% of patients with bacteremic pneumococcal pneumonia died.² The introduction of sulfas and penicillin in the mid-20th century, subsequent refinements in antibiotic chemotherapy, and improvements in supportive care rendered pneumococcal disease readily treatable, notwithstanding the threat of antibiotic-resistant pneumococcus.³ Despite the availability of effective antibiotic therapy against S pneumoniae, pneumococcal disease remains a significant cause of morbidity and mortality among people with increased susceptibility, such as older adults and those living with chronic illness or immunosuppressive conditions. In developed countries like the U.S., where a growing portion of the population is vulnerable to S pneumoniae by virtue of their advanced age and underlying medical conditions, pneumococcal disease is still an important public health concern.⁴

Penumococcal Vaccines: A Long Time Coming

Vaccination against S pneumoniae has proven an efficacious strategy to reduce the morbidity and mortality associated with this pathogen.⁵ The original efforts to develop a pneumococcal vaccine culminated in 1945 with a vaccine containing pneumococcal capsular polysaccharides, which elicited a protective immune response among U.S. soldiers (Table 1).Subsequent investigations determined that the protective response was specific to pneumococcal disease caused by the 4 pneumococcal capsular serotypes included in the vaccine, that the carrier rate of pneumococcus with the vaccine serotypes decreased by about 50%, and that the incidence of pneumonia from the vaccine serotypes was reduced even in nonimmunized soldiers.⁶ These early observations remain relevant to our contemporary understanding of the impact of pneumococcal vaccination: Protection is limited to serotypes included in the vaccine; the vaccine reduces colonization; and the vaccine leads to herd immunity—the protection of unvaccinated subjects.

Despite this achievement, the use of vaccines as a strategy to combat pneumococcal disease was upstaged in the subsequent decades by the success of antibiotics. Renewed interest in pneumococcal vaccines resulted from the efforts of Robert Austrian, MD, who astutely observed that “highly effective antimicrobial drugs must be supplemented by other measures, both prophylactic and therapeutic, if the significant mortality resulting still from pneumococcal infection is to be reduced.”⁷

After initial studies carried out in South African gold miners, the FDA approved a pneumococcal polysaccharide vaccine (PPSV) against 23 of about 90 circulating serotypes.⁸ The CDC and the Advisory Committee on Immunization Practices (ACIP) initially recommended PPSV-23 for persons perceived to be at high risk for pneumococcal disease, including those with chronic diseases, immunocompromising conditions, and older adults.⁹

Three decades later, the analysis of a large body of available evidence demonstrated the protective effects of PPSV-23 against invasive pneumococcal disease caused by pneumococcal types included in the vaccine, especially bacteremic pneumonia (about 75% reduction, odds ratio [OR] 0.26, 95% confidence interval [CI] 0.14-0.45).¹⁰ A perceived shortcoming of PPSV-23, which some experts dispute, is the lack of definite protection against nonbacteremic pneumococcal pneumonia.¹¹ Studies of nursing home residents demonstrated a 50% reduction in the incidence of both pneumococcal pneumonia and all-cause pneumonia, suggesting that PPSV-23 offers protection against noninvasive pneumococcal pneumonia in specific populations.¹² Additional potential limitations of PPSV-23 include reduced benefit in patients aged > 65 years and waning of protection over time.¹³

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Protein-Conjugate Vaccines

Clearly, the most important limitation of PPSV-23, inherent to all capsular polysaccharide vaccines, is that it does not elicit an immune response in children aged < 2 years. The successful development of a vaccine against Haemophilus influenzae type b (Hib) gave rise to a new generation of pneumococcal vaccines.¹⁴ Specifically, the Hib vaccine covalently binds, or conjugates, the capsule polysaccharide to an antigenic protein, leading to effective T-cell–mediated antibody production in infants and toddlers.

In 2000, children received the first iteration of a protein-conjugate vaccine containing the 7 most relevant pneumococcal serotypes (PCV-7).¹⁵ The effects of PCV-7 on pneumococcal disease have been extraordinary, practically eliminating infections caused by the pneumococcal serotypes included in the vaccine. Immunizing children with PCV-7 also ushered in a fundamental public health benefit for adults aged > 65 years: a reduction of nearly 90% in the incidence of pneumococcal infections caused by serotypes included in the vaccine. By eliciting mucosal immunity, which leads to decreased nasal carriage of the covered pneumococcal strains among children, PVC-7 generates herd immunity, leading to reductions in transmission, colonization, and infection with vaccine serotypes among adults.¹⁶

In 2010, a conjugate vaccine containing 13 serotypes (PCV-13) replaced PCV-7 administration for children.^17,18 The PCV-13 is expected to protect children and the herd from disease caused by 6 additional pneumococcal serotypes, including those that surged as replacement strains, filling the ecologic niche created by PCV-7, such as the epidemiologically relevant serotype 19A.^19,20