The FDA granted Breakthrough Therapy Designation for a 20-Valent Pneumococcal Conjugate Vaccine (20vPnC) in development at Pfizer on September 20, 2018. Its proposed indication is prevention of invasive disease and pneumonia caused by 20 S. pneumoniae serotypes in adults age 18 years and older. Preliminary clinical evidence suggested that this vaccine may have substantial advantages over available vaccines. In 2017 the FDA also granted Fast Track status for a pediatric indication for 20vPnC.

The health care community has high expectations for a new vaccine with broader coverage, as S. pneumoniae is a significant human pathogen. It is a primary cause of community-acquired pneumonia and meningitis in children and the elderly.

Vaccines are now administered routinely to children, and are also available to adults. However, the vaccines only cover a limited number of this bacteria’s roughly 91 strains. As infection from 1 strain declines, other strains often change under the pressure of immunization and become more common or virulent.

At the 29th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Amsterdam, Netherlands, researchers updated attendees with recent findings about this vaccine, currently designated by the lab name PF-06482077. PF-06482077 augments the 13 serotypes contained in Pfizer's pneumococcal 13-valent conjugate vaccine (Prevnar 13) with 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F).

The study presented in Amsterdam was a phase 2 randomized, active-controlled, double-blinded trial (N=444). All participants were ages 60 to 64 years. Participants received PF-06482077 followed by placebo at 1 month, or the pneumococcal 13-valent conjugate vaccine followed by 23-valent polysaccharide vaccine at 1 month.

Immunity against pneumococcus is mediated by phagocytosis in the presence of complement and antibodies to pneumococcal capsular polysaccharides. In vitro, serum antibodies’ opsonophagocytic activities mimic the antibodies’ functional activities in vivo.  Researchers use opsonophagocytic activity to predict protective immunity.

In this study, the researchers observed robust responses for all 20 vaccine serotypes in the 20vPnC group. Using opsonophagocytic activity as a measure, they saw geometric mean fold-rises from baseline ranging from 6.1 to 68.6 for the serotypes in common with pneumococcal 13-valent conjugate vaccine, and 9 to 112.2 for the 7 additional serotypes not included in that drug.

Adverse events were in keeping with what we have come to expect from immunizations, mainly mild injection site reactions (redness, swelling, pain).

The 20 serotypes included in 20vPnC are responsible for the majority of circulating pneumococcal disease in adults. As noted, infection with these serotypes often leads to serious disease and morbidity. Many of these serotypes are also associated with antibiotic resistance. Compared with invasive disease, noninvasive disease (middle-ear infection, sinusitis or recurrent bronchitis) is usually less severe, but considerably more common.

20vPnC entered phase 3 clinical trials in December 2018. If approved, this vaccine with have considerable impact in the United States and around the world.


References
  1. Pfizer announces presentation of data from a phase 2 study of its 20-valent pneumococcal conjugate vaccine candidate being investigated for the prevention of invasive disease and pneumonia in adults aged 18 years and older [news release]. April 13, 2019: Pfizer news. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_announces_presentation_of_data_from_a_phase_2_study_of_its_20_valent_pneumococcal_conjugate_vaccine_candidate_being_investigated_for_the_prevention_of_invasive_disease_and_pneumonia_in_adults_aged_18_years. Accessed April 15, 2019.
  2. Balsells E, Guillot L, Nair H, Kyaw MH. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis. PLoS One. 2017 May 9;12(5):e0177113.
  3. Soininen A, Karpala M, Wahlman SL, Lehtonen H, Käyhty H. Specificities and opsonophagocytic activities of antibodies to pneumococcal capsular polysaccharides in sera of unimmunized young children. Clin Diagn Lab Immunol. 2002;9(5):1032-1038.