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Dengue (DENV) is a mosquito-borne virus with four serotypes causing substantial morbidity in tropical and subtropical areas worldwide. V181 is an investigational, live, attenuated, quadrivalent dengue vaccine. In this phase 1 double-blind, placebo-controlled study, the safety, tolerability, and immunogenicity of V181 in baseline flavivirus-naïve (BFN) and flavivirus-experienced (BFE) healthy adults were evaluated in two formulations: TV003 and TV005. TV005 contains a 10-fold higher DENV2 level than TV003. Two-hundred adults were randomized 2:2:1 to receive TV003, TV005, or placebo on Days 1 and 180. Immunogenicity against the 4 DENV serotypes was measured using a Virus Reduction Neutralization Test (VRNT 60 ) after each vaccination and out to 1 year after the second dose. There were no discontinuations due to adverse events (AE) or serious vaccine-related AEs in the study. Most common AEs after TV003 or TV005 were headache, rash, fatigue, and myalgia. Tri- or tetravalent vaccine-viremia was detected in 63.9% and 25.6% of BFN TV003 and TV005 participants, respectively, post-dose 1 (PD1). Tri- or tetravalent dengue VRNT 60 seropositivity was demonstrated in 92.6% of BFN TV003, 74.2% of BFN TV005, and 100% of BFE TV003 and TV005 participants PD1. Increases in VRNT 60 GMTs were observed after the first vaccination with TV003 and TV005 in both flavivirus subgroups for all dengue serotypes, and minimal increases were measured PD2. GMTs in the TV003 and TV005 BFE and BFN groups remained above the respective baselines and placebo through 1-year PD2. These data support further development of V181 as a single-dose vaccine for the prevention of dengue disease.

In most countries worldwide, pneumococcal conjugate vaccines have been included in the infant immunization program, resulting in a significant reduction in the burden of pneumococcal disease in children and adults. Shifting serotype distribution due to the indirect effect of infant vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) may continue to increase the gap between 23-valent pneumococcal polysaccharide vaccine (PPSV23) and PCV13 serotype coverage for older adults in the coming years. This clinical study (V110-029; NCT02225587) evaluated the safety and immunogenicity of sequential administration of PCV13 followed approximately 8 weeks later, or approximately 26 weeks later, by PPSV23 in healthy adults ≥50 years of age. Both dosing intervals were generally well tolerated as measured by the nature, frequency, and intensity of reported adverse events (AEs) in both vaccination groups. Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) measured 30 days following receipt of PPSV23 in either group and at Week 30 were generally comparable between the 2 groups for 6 serotypes unique to PPSV23 and 12 serotypes shared between PCV13 and PPSV23, regardless of the interval between receipt of PCV13 and PPSV23. In addition, administration of PPSV23 given either 8 weeks or 26 weeks following PCV13 did not negatively impact immune responses induced by PCV13. Furthermore, administration of PPSV23 given either 8 weeks or 26 weeks after PCV13 elicited serotype-specific OPA GMTs to serotypes unique to PPSV23, which could provide earlier protection against pneumococcal disease caused by these serotypes in comparison with the current Advisory Committee on Immunization Practices recommended interval of at least 12 months.

Open-label, multicenter, randomized study (NCT00289913) evaluated immunogenicity, safety, and tolerability of Vaqta (hepatitis A vaccine) administered with PedvaxHIB (Haemophilus b conjugate vaccine [Meningococcal protein conjugate]) & Infanrix (diphtheria/tetanus/acellular pertussis vaccine) in healthy, 15-month-old children. Five groups were evaluated: Group 1 received Vaqta/Infanrix PedvaxHIB on Day-1 and Vaqta at Week-24; Group 2 received Infanrix PedvaxHIB on Day-1, Vaqta at Week-4, and Vaqta at Week-28; Group 3 received Vaqta/PedvaxHIB on Day-1 and Vaqta Week-24; Group 4 received PedvaxHIB on Day-1, Vaqta at Week-4, and Vaqta at Week-28; and Group 5 (safety only) received Vaqta on Day-1 and Vaqta at Week-24. Hepatitis A seropositivity rate (SPR: ≥10 mIU/mL), Hib capsular polyribosylribitol phosphate (PRP) antibody response (>1.0 μg/mL), and geometric mean titers (GMT) to pertussis toxin (PT), pertussis filamentous hemagglutinin antibody (FHA), and pertactin were examined. Non-inferiority statistical criteria required a difference >10% in Hepatitis A SPR, PRP >1.0 μg/mL, and a GMT ratio of >0.67 for pertussis antigens. Injection-site and systemic adverse events (AEs) and daily temperatures were collected. Hepatitis A SPRs were 100% for Groups 1-4, regardless of initial serostatus. Anti-PRP titers were comparable (98.1% - 97.0%) for Groups 1-4. GMT and mean fold-rise were comparable for all 3 pertussis antigen components between concomitant and nonconcomitant groups. Criteria for non-inferiority of immune responses for concomitant vs nonconcomitant administration were met for Hepatitis A, Hib, and pertussis antigens. No statistically significant incidence differences of individual AEs were found between concomitant and nonconcomitant groups. No serious vaccine-related AEs or deaths were reported; no subject discontinued due to an AE. Immune responses to Vaqta, PedvaxHIB, and Infanrix given concomitantly were non-inferior to nonconcomitant responses. Vaqta administered with PedvaxHIB & Infanrix had an acceptable safety profile in 15-month-old children.