A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants

Abstract

Background: Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of 2 clinical lots of V114 (investigational 15-valent pneumococcal vaccine: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F*, 23F, 33F*) to 13-valent pneumococcal conjugate vaccine (PCV13) in healthy infants (*serotypes unique to V114). Methods: Healthy infants 6–12 weeks old were randomized to receive a 4-dose regimen of V114 Lot 1, V114 Lot 2 or PCV13 at 2, 4, 6 and 12–15 months old. Adverse events were evaluated after each dose. Primary immunogenicity endpoint was to demonstrate noninferiority of V114 Lot 1 and V114 Lot 2 relative to PCV13 based on proportion of infants achieving serotype-specific IgG concentration ≥0.35 µg/mL for 13 serotypes shared with PCV13 at 1 month postdose 3 (PD3). Serotype-specific IgG geometric mean concentrations (GMCs) for all 15 V114 serotypes were measured at PD3, predose 4 and 1 month postdose 4 (PD4). Results: Overall, 1044 of 1051 randomized infants received ≥1 dose of vaccine (V114 Lot 1 [n = 350], V114 Lot 2 [n = 347] or PCV13 [n = 347]). Adverse events were generally comparable across groups. At PD3, both V114 lots met noninferiority criteria for all 13 serotypes shared with PCV13. IgG GMCs were comparable among V114 and PCV13 recipients at PD3 and PD4. Serotype 3 responses were higher following receipt of V114 than PCV13. Both V114 lots induced higher GMCs than PCV13 to the 2 unique V114 serotypes. Conclusions: Immunogenicity of both V114 lots was noninferior to PCV13 for all 13 shared serotypes between the 2 vaccines and displayed comparable safety and tolerability profiles to PCV13.

Pneumococcal Disease Prevention: Are We on the Right Track?

“…Two vaccines containing 15 [ 6 ] and 20 STs [ 7 ] are in advanced development and were found immunogenic and safe. However, even if they were licensed for use in humans, it seems highly unlikely that they can definitively solve the problem of S. pneumoniae infection prevention.…”

“…The 20-valent vaccine is produced by the same manufacturer of PCV13 and does not differ in ST3 content. It has been reported that the 15-valent vaccine evokes a more sustained antibody response against ST3 than PCV13 [ 6 ]. However, analysis of the results of the study carried out in infants receiving the four-dose immunization schedule reveals that antibody concentrations achieved after PCV15, despite being higher than those obtained with PCV13 after both the primary series and the booster dose, remain much lower than the putative correlate of protection.…”

High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides

“…Current PCV formulations include vaccine-serotypes (VT) 6A (PCV13), 6B and 18C (PCV13, PCV10). Serotype 22F is included in next-generation PCV15 and PCV20 2 , 3 . Before the introduction of PCVs, serogroup 6 was associated with 14–18% of invasive pneumococcal disease (IPD) episodes worldwide, whereas serotype 18C was the fifth most common serotype identified in IPD cases in developed nations 4 , 5 .…”

Effect of prophylactic administration of antipyretics on the immune response to pneumococcal conjugate vaccines in children: a systematic review

“…The incidence of some events like febrile seizures seems to occur more frequently when PCVs are co-administered with other routine vaccines [11]. There are concerns, also, that the reactogenicity of PCVs may increase by the insertion of more serotypes in the new conjugated vaccine formulations, created to deal with the "serotype replacement" phenomenon [12][13][14].…”