As pneumococcal polysaccharide vaccines were found to be ineffective in children under the age of two, vaccine development continued. Pneumococcal related deaths were reported to be uncommon among children except in the case of immune suppression, meningitis, or severe bacteremia following the removal of the spleen, but children two and under, along with adults 65 and older, were still considered by health officials to be at a higher risk for pneumococcal infections.
Development of a method to bind a polysaccharide with a carrier protein to enhance the immune response began in 1980, and in 1987, the conjugated Hib vaccine became the first vaccine using polysaccharide-protein conjugation technology to receive approval by the FDA.
Wyeth Lederle was the first vaccine manufacturer to develop a pneumococcal conjugate vaccine, Prevnar 7. In pre-licensing clinical trials, Prevnar 7 (PCV7) was tested against an experimental meningitis C vaccine, an “active” control that called into question the scientific validity of the trial. The vaccine, however, still received approval by the FDA in February of 2000.
The 7-valent pneumococcal conjugate vaccine contained Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, each of which are individually conjugated to diphtheria CRM197 protein and were approved for use in infants and children at 2, 4, 6, and 12-15 months of age for the prevention of invasive disease caused by Streptococcus pneumoniae from the strains found within the vaccine.
On June 21, 2000, the CDC’s ACIP voted to recommend PCV7 vaccine for use in all children 23 months of age and younger, as well as in children ages 24 to 59 months considered to be at high-risk of serious pneumococcal infection.
The highly successful promotion by Wyeth Lederle, the CDC, and the American Academy of Pediatrics (AAP) made Prevnar (PCV7) the best-selling new pharmaceutical product of 2000, generating $461 million in sales.
By 2001, however, PCV7’s popularity, in conjunction with manufacturing issues, resulted in vaccine shortages. The shortages required ACIP to temporarily revise PCV7 vaccine recommendations, prioritizing the vaccine’s use for children most at risk for pneumococcal disease. Issues with vaccine shortages were not completely resolved until September of 2004.
In October 2002, the FDA approved PCV7 for use in the prevention of middle ear infections (otitis media) despite clinical studies noting the vaccine to be only seven percent effective against all types of acute otitis media.
Following PCV7 introduction on a global scale, scientists began to report that while the vaccine appeared to be effective in reducing nasopharyngeal carriage of S. pneumoniae strains found within the vaccine, this reduction had resulted in a significant increase in non-vaccine type strains, most notably, strain 19A, a highly virulent and antibiotic-resistant serotype. In Spain, an increase in invasive pneumococcal disease occurred following the introduction of PCV7, with the emergence of several non-vaccine type strains.
