Vaccine 20 (2002) 2404–2409 Placental and breast transfer of antibodies after maternal immunization with polysaccharide meningococcal vaccine: a randomized, controlled evaluation Nigar S. Shahid a,∗ , Mark C. Steinhoff b , Eliza Roy a , Tahmina Begum a , Claudette M. Thompson c , George R. Siber d a Child Health Programme, Public Health Sciences Division, ICDDR,B: Centre for Health and Population Research, G.P.O. Box 128, Dhaka 1000, Bangladesh b Department of International Health and Epidemiology, School of Public Health; Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA c Harvard School of Public Health, Boston, MA, USA d Wyeth-Lederle Vaccines, Pearl River, NY, USA Received 7 March 2001; received in revised form 21 December 2001; accepted 22 December 2001 Abstract We evaluated the strategy of maternal immunization with Neisseria meningitidis (Nm) vaccine in Asian mothers, to assess potential protection of infants, including by breast milk. One hundred and fifty-seven women in the third trimester were randomized to receive a single dose of the polysaccharide Nm (n = 75) or a control vaccine (n = 82). Group A Nm IgG levels were measured in maternal and infant sera, and specific IgA in breast milk. A 5.6-fold rise of Nm IgG antibody was observed among the Nm vaccinees. At delivery, geometric mean titres (GMTs) of Nm IgG antibody in Nm mothers was 12.5 g/ml versus 4.97 g/ml, with a mean infant/maternal antibody ratio of 0.56. Infants of Nm vaccinees had mean IgG levels of 6.9, 2.3, 1.2 and 0.6 g/ml at 0, 6, 14 and 22 weeks, significantly higher than in control children up to 14 weeks. Anti-Nm IgA levels in milk were 6.8 to 2.0 g/ml, significantly higher in Nm vaccinees till 6 months. Immunization during pregnancy is safe for both mothers and infants, and provides infants with significantly increased levels of specific IgG for 2–3 months and oral IgA for 6 months. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: Maternal immunization; Meningococcal vaccine; Placental transfer; Passive immunity; Breast milk 1. Introduction Neisseria meningitidis (Nm) causes epidemics of menin- gitis and sepsis, and is a much feared public health emer- gency [1]. In high income countries where the disease is mostly endemic, the annual incidence rate varies between 1 and 12 per 100,000 population but may reach 10–20 per 100,000, however, rates >200 per 100,000 population are ob- served during epidemics in non-industrialized regions [2–4]. Young infants are at the highest risk: the endemic incidence in infants under 3 months of age is 2.5 times higher than the rates in the age group of 12–23 months in USA [3]. Group A and C meningococcus strains have caused extensive epi- demics in the Americas, the African continent, the Middle East and the Indian subcontinent between 1987 and 1990 [5,6]. Epidemics in Saudi Arabia occur during the Haj [5]. ∗ Corresponding author. Fax: +880-2-8826050/8823116. E-mail address: nshahid@icddrb.org (N.S. Shahid). Serious maternal and neonatal illnesses with Nm in preg- nancy have also been reported [7,8]. In developing countries outside of Africa there is paucity of data on the incidence of the disease in early infancy due to Nm. However, a re- cent hospital report from Bangladesh reports that Nm was the third most common bacterial isolate in CSF specimens in infants with meningitis [9]. The report also observes that 25% of the total cases of Nm meningitis occurred in infants <6 months of age. Maternal immunization is a strategy with the potential to provide passive protection to infants during the vulnerable first few months of life before active immunization of the in- fant is feasible. Immunogenicity and safety trials of maternal gestational immunization for meningococcal polysaccharide vaccines have been reported from the Americas and Africa [10–13]; these showed no major side effects, relatively good immunogenicity, but did not report breast milk antibody. Our goal in this trial was to prospectively assess the safety and immunogenicity of the licensed quadrivalent meningo- 0264-410X/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0264-410X(02)00061-0