Newborn vaccination : how early can we protect and how long does protection last?

Abstract

Background The challenge for infant vaccination is to protect as early as possible and to maintain immunity as long as possible. At present only three vaccines are given at birth, oral polio vaccine (OPV), hepatitis B (HBV) and Bacille Camille Guerin (BCG). Although the youngest infants are at greatest risk of death or hospitalisation from pertussis, the earliest age the first pertussis containing vaccine is currently given is at 6 weeks. Few studies examining newborn responses to acellular pertussis vaccine exist and no studies have examined 2 doses of monovalent acellular pertussis (Pa) vaccine before 8 weeks old. The first groups to receive HBV vaccine in Australia were Indigenous infants and those born to mothers from countries with high endemicity of HBV. The duration of protection afforded by infant HBV vaccination is not definitively known beyond 15 years and its determination has important worldwide implications on whether booster doses are required following infant vaccination. No studies have examined long-term (> 10 years) HBV immunity following infant HBV vaccination in Australia.

Aim The aim of this thesis is to examine responses to early life (neonatal) vaccination, in particular acellular pertussis vaccine, and the longevity of immunity, in particular following HBV vaccine in infancy.

Methods Clinical vaccine trials examining early life responses to acellular pertussis vaccine and longevity of HBV immunity were conducted. Neonatal responses to acellular pertussis (Pa) vaccine: 76 newborns were randomized to 3 different vaccine groups: (1) Pa at birth and one month or (2) at birth only or (3) controls. All received Hepatitis B vaccine (HBV) at birth and combination vaccines which included diphtheria, tetanus, Haemophilus influenzae type b, Hepatitis B and polio antigens with conjugate pneumococcal vaccine at 2, 4 and 6 months. IgG antibody responses to pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) were measured in maternal serum and at 2, 4, 6 and 8 months of age. Antibody responses to concomitant antigens, hepatitis B, Hib, diphtheria and tetanus were measured at 8 months. Cell mediated immunity to pertussis was also measured on the 8 month sample. Adverse events were recorded by parental diary and active telephone follow-up for 7 days after each vaccination. Long term immunity to HBVvaccine: Clinical vaccine studies were conducted in two different cohorts (i) Study 1: Children and adolescents over 10 years of age born to ‘at risk’ mothers targeted for HBV vaccination because of their ethnicity (n=120) (ii) Study 2: Indigenous adolescents, age 16-20 years, in the Northern Territory, Australia (n=43 7) Duration of HBV protection was measured by rates of chronic HBV infection in those vaccinated in infancy and booster responses to HBV vaccine. HBV serology was measured at baseline, including hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti—HBc) and hepatitis B surface antigen (HBsAg) as a marker of the prevalence of HBsAg carriage. Anamnestic booster response was defined as a rise in anti-HBs level to >10mIU/ml in those with non detectable levels pre—booster or a 4 fold increase in anti-HBs level in those with detectable levels pre booster. HBV vaccine history was collected from individual child health records, healthcare provider/ community healthcare clinic records and electronic immunisation registers. Indigenous adolescents (study 2) were asked additional questions relating to current or past substance use (cigarettes, alcohol marijuana, petrol sniffing). Anamnestic responses were measured 2-4 weeks after a booster dose of a recombinant 10ug HBsAg vaccine.