Immunogenicity and Safety of Monovalent Acellular Pertussis Vaccine at Birth

Nicholas Wood,Peter Richmond,Terry Nolan,Helen Marshall,Kirsten Perrett,Emma Gibbs,Peter Mcintyre

doi:10.1001/jamapediatrics.2018.2349

Abstract

ImportanceAn alternative option to maternal vaccination to prevent severe pertussis in infants is vaccination at birth. Data are needed on the immunogenicity and safety of a birth dose of monovalent acellular pertussis (aP) vaccine.ObjectiveTo compare IgG antibody responses to vaccine antigens at 6, 10, 24, and 32 weeks of age between newborn infants receiving the aP vaccine and hepatitis B vaccine (HBV) or HBV alone.Design, Setting, and ParticipantsA randomized clinical trial was conducted at 4 sites in Australia (Sydney, Melbourne, Adelaide, and Perth) between June 11, 2010, and March 14, 2013, among 440 healthy term (>36 weeks’ gestation) infants aged less than 5 days at recruitment. Statistical analysis was performed from March 1, 2015, to June 2, 2016.InterventionNewborns received HBV and, after stratification by maternal receipt of adult-formulated aP-containing vaccine (tetanus toxoid, reduced diphtheria toxoid, and pertussis antigen content [Tdap]) prior to pregnancy, were block randomized to receive the aP vaccine (without diphtheria or tetanus) within 5 days of birth or not. At 6, 16, and 24 weeks, infants received a hexavalent vaccine with pediatric-formulated diphtheria, tetanus and pertussis antigens (DTaP), Haemophilus influenzae type b (Hib), HBV, and polio vaccine, as well as the 10-valent pneumococcal conjugate vaccine.Main Outcomes and MeasuresDetectable (>5 enzyme-linked immunosorbent assay units per milliliter) and geometric mean concentrations of IgG antibody to pertussis toxin (PT), pertactin, and filamentous hemagglutinin at 6, 10, and 24 weeks stratified by maternal Tdap history, and antibody at 32 weeks to HBV, Hib, polio, diphtheria, tetanus, and pneumococcal serotypes. The primary outcome was detectable IgG to both PT and pertactin at 10 weeks.ResultsA total of 440 infants (207 girls and 233 boys; median gestation, 39.2 weeks) were randomized to receive the aP vaccine plus HBV (n = 221) or HBV only (control group; n = 219). At 10 weeks, 192 of 206 infants who received the aP vaccine (93.2%) had detectable antibodies to both PT and pertactin vs 98 of 193 infants in the control group (50.8%) (P < .001), with the geometric mean concentration for PT IgG 4-fold higher among the group that received the aP vaccine. At age 32 weeks, all infants (n = 181 with sera available for testing) who received the aP vaccine at birth had detectable PT IgG and significantly lower IgG geometric mean concentrations for Hib, hepatitis B, diphtheria, and tetanus antibodies. Local and systemic adverse events were similar between both groups at all time points.Conclusions and RelevanceThe monovalent aP vaccine is immunogenic and safe in neonates and, if licensed and available, would be valuable for newborns whose mothers did not receive the Tdap vaccine during pregnancy.Trial Registrationhttp://anzctr.org.au Identifier: ACTRN12609000905268

Highlights

MethodsStudy Design and Participants This phase 3 randomized, nonblinded clinical trial of the administration of monovalent acellular pertussis (aP) vaccine to newborns was conducted between June 11, 2010, and March 14, 2013, in 4 cities in Australia (Sydney, Melbourne, Perth, and Adelaide)
These results indicate that a birth dose of acellular pertussis (aP) vaccine is immunogenic in newborns and significantly narrows the immunity gap between birth and 14 days after receipt of DTaP at 6 or 8 weeks of age, marking the critical period when infants are most vulnerable to severe pertussis infection
Our study has shown that a dose of aP vaccine at birth was immunogenic and safe and may induce earlier protection[3] through generating “active” humoral immunity

Summary

Methods

Study Design and Participants This phase 3 randomized, nonblinded clinical trial of the administration of monovalent aP vaccine to newborns was conducted between June 11, 2010, and March 14, 2013, in 4 cities in Australia (Sydney, Melbourne, Perth, and Adelaide). Appropriate regulatory and ethical approval was granted by the Clinical Trial Notification Scheme, Therapeutic Goods Administration, Department of Health and Ageing, Australian Government; Sydney Children’s Hospitals Network Human Research Ethics Committee; Royal Children’s Hospital, Melbourne Human Research Ethics Committee; Women’s and Children’s Hospitals, Adelaide, Human Research Ethics Committee; and Princess Margaret Hospital for Children Human Research Ethics Committee. The trial was registered on the Australian New Zealand Clinical Trials Registry and was reported using CONSORT guidelines. Mothers of eligible infants were approached in antenatal clinics or postnatal wards in participating hospitals.

Results

Discussion

Conclusion