This article is more than 5 years old. Information may no longer be current.

PCV13 increases protection against pneumococcal disease

Yeh SH. Pediatrics. 2010;126:e493-e505.

Infants and toddlers respond well to the 13-valent pneumococcal conjugate vaccine, data published online this week indicate.

Researchers from Wyeth and several institutions conducted a phase 3, randomized, double-blind, active-controlled trial at 38 sites in the United States that compared the safety and efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar, Wyeth) with the seven-valent pneumococcal conjugate vaccine (PCV7, Prevnar, Wyeth).

The researchers enrolled 666 infants between September and December 2006 and completed 6-month follow-up by June 2008. Data on immunogenicity were available for 504 infants and 462 toddlers, and data on safety was available in 663 children.

At 2, 4 and 6 months, infants received 0.5 mL of PCV13 or PCV7 at each visit along with the diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B and inactivated poliovirus vaccine (DTaP-HepB-IPV, Pediarix, GlaxoSmithKline) and the Haemophilus influenzae type B conjugate vaccine (Hib, ActHIB, Sanofi Pasteur).

Between 12 and 15 months, toddlers also received a 0.5-mL dose of PCV13 or PCV7 as well as the measles, mumps, rubella and varicella vaccine (MMRV, ProQuad, Merck), Hib (PedvaxHIB, Merck) and the hepatitis A vaccine (HepA, Vaqta, Merck).

After administration of the infant doses, PCV13 and PCV7 were comparable regarding coverage of five of the seven common serotypes contained in PCV7. Serotypes 6B and 9V were the exceptions.

Geometric mean concentrations (GMCs) of antipolysaccharide immunoglobulin G (IgG) responders for all seven serotypes induced by PCV13 appeared noninferior, although they were generally lower than those observed in children receiving PCV7. Serotype-specific opsonophagocytic antibody activity was also comparable between the two vaccine groups.

PCV13 also induced greater anticapsular polysaccharide-binding IgG levels and functional antibody activity against the six additional serotypes — 1, 3, 5, 6A, 7F and 19A — contained in the vaccine compared with PCV7.

After the toddler dose, antibody levels increased further, according to the researchers, with IgG GMCs to the seven common serotypes in the PCV13 group demonstrating noninferiority to those in the PCV7 group.

PCV13’s safety profile also appeared on par with PCV7, the researchers said. Most adverse events were mild in severity and generally reflected anticipated childhood illnesses. One serious adverse event in each group, including pyrexia with febrile convulsion among those receiving PCV13 and nephroblastoma among those receiving PCV7, occurred after infant dosing.

“PCV13 has a safety profile comparable to PCV7,” the researchers wrote. “In addition, PCV13 should mediate protection against the six additional serotypes, all of which are important worldwide causes of severe pneumococcal disease.”

In July, the AAP issued a policy statement recommending that PCV13 replace PCV7 for routine immunization and offered guidelines for vaccination schedules and use in certain populations.

The inventor of the first polysaccharide pneumococcal vaccine was Dr. Robert Austrian at the University of Pennsylvania. In response to the difficulties encountered in developing the 23-valent vaccine, Austrian said that it was "the equivalent of 23 different vaccines in one shot." Developing the conjugate pneumococcal polysaccharide vaccine has been even more difficult. Manufacturers have to take into account the facts that pneumococcal polysaccharides from different serotypes are not equally immunogenic, requiring different quantities in the final vaccine; that the chemistry of conjugation is slightly different for different polysaccharides, and that combination can induce slightly different immune responses compared with individual components administered separately. These problems are generally not appreciated by clinicians. The study by Yeh and coworkers shows that PCV13 safely induces excellent immune responses against each of the components contained in the vaccine. PCV13 will provide greater protection than that afforded by PCV7, especially against strains such as 19A that emerged post-licensure.

– Paul Offit, MD
Infectious Diseases in Children Editorial Board