Background

An antenatal pertussis vaccination programme was introduced in 2012 in the UK following a national outbreak of pertussis. Two DTaP-IPV vaccines were recommended; REPEVAX® (2012-2014) and BOOSTRIX® (2014 onwards). Following antenatal vaccination, a lower antibody response to primary immunisation was shown in infants, known as blunting, but the longer-term effects of this have not been documented in the UK where the first DTAP-IPV booster is given pre-school at the age of 40 months. The study aims to compare antigen-specific IgG geometric mean concentrations (GMCs) before and after the preschool booster in children whose mothers did or did not receive a pertussis-containing antenatal vaccine.

Methods

This was a phase IV extension study, funded by the NIHR policy research programme, comparing vaccine responses in children receiving the preschool booster (REPEVAX®), whose mothers were randomised to one of two pertussis-containing antenatal vaccines (BOOSTRIX® or REPEVAX®), or no pertussis-containing antenatal vaccine (control). Blood samples were obtained prior to and 1 month after the preschool booster. Pre- and post-vaccination IgG GMCs of anti-pertussis toxin (PT), anti-filamentous haemagglutinin (FHA), anti-fimbriae 2 & 3 (FIM), anti-diphtheria and anti-tetanus toxoid were compared.

Results

64 children were recruited; 26, 22 and 16 in the BOOSTRIX, REPEVAX and control groups respectively. The difference in IgG GMCs pre- and post-vaccination between the vaccinated groups was not statistically significant. The difference in IgG GMCs between the vaccinated and control groups was only statistically significant for anti-PT in the BOOSTRIX group pre-vaccination (Table 1).

Conclusions

To our knowledge, this is the first study to explore the influence of antenatal pertussis vaccination on children’s antibody response beyond 2 years of age. The impact of blunting post-primary immunisation can persist until preschool age, although the clinical significance remains unclear.

Clinical Trial Registration

Clinical trial registration: ClinicalTrials.gov Identifier NCT03578120

Background

A safe and effective vaccine against cytomegalovirus (CMV) infection is a high priority in the effort to prevent congenital CMV. We present interim safety and immunogenicity data from a Phase 1 trial of mRNA-1647, a mRNA-based vaccine encoding CMV pentamer complex (PC) and glycoprotein B (gB) antigens.

Methods

This Phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study is assessing the safety and immunogenicity of mRNA-1647 administered on a 0, 2, 6-month schedule in 154 CMV-seronegative and CMV-seropositive healthy adults aged 18-49. Safety and immunogenicity through 1 month post-third vaccination in 30, 90, and 180µg treatment groups and through 1 month post-second vaccination in the 300µg treatment group is presented. Immunogenicity is reported as PC- and gB- specific neutralizing antibody (nAb) titers.

Results

The most common solicited local adverse reaction (AR) was injection site pain. The most common solicited systemic ARs were headache, fatigue, myalgia and chills. Neutralizing antibody titers increased in a dose-dependent manner in both CMV-seronegative and CMV-seropositive participants. In CMV-seronegative participants post-third vaccination, PC-specific nAb titers were up to 10-fold higher and gB-specific nAb titers up to 1.4-fold higher than that of natural CMV infection. In CMV-seropositive participants post-third vaccination, PC-specific nAb titers were up to 40-fold over baseline and gB-specific nAb titers were up to 6-fold over baseline. The 300μg mRNA-1647 treatment group continued to demonstrate a dose-dependent increases in nAb titers post-second vaccination.

Conclusions

These phase 1 interim data indicate that mRNA-1647 was generally well-tolerated, induced nAb responses exceeding that of natural CMV infection in CMV-seronegative participants, and substantially boosted nAb titers in CMV-seropositive participants. This first-in-human trial demonstrates the potential of mRNA-1647 to prevent CMV infection.

Clinical Trial Registration

ClinicalTrials.gov NCT03382405

Background

Maternal vaccination helps protect infants from infections in their first months of life but can interfere with infant and toddler immune responses to some pediatric vaccines. A descriptive analysis (on data from two follow-up studies of a randomized pertussis maternal immunization study) was performed to assess the impact of different primary series dosing schedules on interference with pertussis responses in infants and toddlers.

Methods

Infants born to mothers who had received reduced-antigen-content diphtheria-tetanus-3-component-acellular-pertussis vaccine (dTpa group) or placebo (control group) during pregnancy (27^0/7–36^6/7 weeks’ gestation) in a phase IV, randomized, observer-blind study were enrolled in primary/booster vaccination follow-up studies. Infants received a 2-dose or 3-dose primary series plus booster with DTPa-HBV-IPV/Hib and 13-valent pneumococcal conjugate vaccine according to local/national immunization schedules. Post-primary and post-booster immune responses to pertussis antigens were evaluated descriptively by primary vaccination schedule (2-dose vs 3-dose).

Results

Of 601 enrolled infants, 528 received 3-dose priming (dTpa group: 264, control: 264; mostly 2-4-6 months) and 73 received 2-dose priming (dTpa group: 32, control: 41; mostly 3-5 months). Trends for lower post-primary vaccine response rates and geometric mean concentrations (GMCs) for pertussis antigens were observed in the dTpa vs control group, both after the 2-dose and 3-dose DTPa-HBV-IPV/Hib primary schedule (Figure-A/B). For both primary vaccination dosing schedules, booster response rates for pertussis antigens were similar between the dTpa and control group (Figure-C), while post-booster GMCs trended lower in the dTpa group for anti-pertussis-toxin and anti-filamentous-hemagglutinin (Figure-D).

Conclusions

These descriptive analyses suggest that interference of maternal pertussis antibodies with infant and toddler immune responses to pertussis antigens occurred both after 2-dose and 3-dose priming. Further studies specifically designed to investigate this are required to confirm these observations.

Funding: GlaxoSmithKline Biologicals SA

Clinical Trial Registration

ClinicalTrials.gov: NCT02377349; NCT02422264; NCT02853929