Immunologic studies of specific mucosal and systemic immune responses in Mexican school children after booster aerosol or subcutaneous immunization with measles vaccine
Introduction
In recent years the need to identify alternative routes of immunization for prevention of infectious diseases has been raised [1], [2]. The basis for this derives from several sources including the requirement for more rapid, reliable, cost-effective, needle-free methods for mass immunization campaigns targeted at the global eradication of infectious diseases such as measles [2]. Previous studies of various routes of measles immunization, which have been summarized in the review by Cutts et al. [2], reported that the aerosolized route had several important advantages. These advantages include public acceptance, low cost and few side effects, including those associated with the transmission of blood-borne pathogens by the re-use of needles compared to the subcutaneous (SQ) route [2]. Of particular importance is that the aerosol (Aer) administration of vaccines is non-invasive, gives good primary serological responses and also appears capable of inducing a good boosting response in contrast to the subcutaneous route. The pioneering studies of Sabin et al. [3], [4] established the utility of aerosol methods of measles immunization in a set of classic studies in Mexican children. These studies not only established the superiority of human diploid vaccine over chick embryo fibroblast derived measles vaccine for aerosol immunization [3] but also suggested that the aerosol route of immunization circumvented the inhibitory effect of maternal antibody on successful immunization [4]. The levels of maternally derived antibody clearly influence responses to both aerosol and injected measles vaccine, except that the former is much less influenced. In contrast to immunization with live vaccines administered by the parenteral route where efficacy is limited by the presence of the maternally-derived serum antibody, the aerosol route appears to be less affected by the presence of transplacentally acquired serum antibody thus allowing the successful vaccination of younger infants, e.g., 6–7 months of age, where measles has the greatest morbidity and mortality. Aerosol administration with measles vaccine has been used in mass campaigns in Mexico administered both as primary and booster regimens to nearly 4 million children with fewer side effects reported than those observed after subcutaneous vaccination [5]. In the South African studies, aerosol administration of Edmonston–Zagreb (EZ) measles vaccine was shown to be more immunogenic than subcutaneous administration of this same vaccine or of Schwarz measles vaccine, at both 1 month and 1 year after vaccination [6], [7]. Antibody titers continued to be substantially higher for the aerosol group at 2 years after vaccination [6]. The results of our Mexican studies confirmed that at 4 months a greater immunogenicity was seen using either aerosol measles vaccination with EZ measles vaccine solely or in combination with rubella vaccine as a booster compared with subcutaneous vaccination with the EZ vaccine or Schwarz measles vaccine [8], [9].
The recognition of the importance of mucosal immunity has increased since the 1960’s, when the critical role of secretory IgA (sIgA) in mucosal immunity was first recognized [10], [11], [12]. Previously, the presence of sIgA specific antibody was reported to be more important in protection against respiratory viral pathogens than serum antibody [13]. Recently, the protective role of IgA in respiratory infections has been questioned since many individuals with selective IgA deficiency are clinically asymptomatic (14) It was also recognized that greater measles-specific antibody responses in serum and nasal secretions were induced in children immunized subcutaneously with live attenuated measles-virus vaccines compared with inactivated measles vaccine [14]. The present report describes the results of a collaborative study which compares the development of measles-specific antibody responses in nasal secretions and sera of school-age children receiving live attenuated measles vaccine as booster dose administered by the subcutaneous route compared with those immunized by the aerosol route.
Section snippets
Study design and subjects
The study was a clinical phase one trial. Forty-nine 6–7-year-old healthy children, from two schools, were arbitrarily divided into either of two groups: (a) 27 children immunized with Edmonston–Zagreb vaccine by the subcutaneous route; and (b) 22 children immunized with EZ vaccine by the aerosol route. Participants had received their primary immunization in infancy but who had not received their booster doses of measles or rubella vaccine and had no previous history of natural measles. After
Results
The baseline characteristics of children in both groups were similar regarding age, sex, baseline titers and previous rubella or measles vaccination or disease.
Discussion
On a global basis, measles continues as a significant and devastating health problem responsible annually for more than 10 million cases and 777,000 deaths. In addition, measles is recognized as one of the leading causes of death for infants and children in developing countries where both malnutrition and a high background of infections caused by other pathogens contribute to the increased morbidity and mortality of the disease.
The recognition of the importance of mucosal immunity in protection
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2014, VaccineCitation Excerpt :Immunization through the mucosal route provides immunological advantages over the injection method, such as the sensitization of the lymphoid tissue dispersed in the mucosa and the production of secretory IgA at a local level [4]. Some clinical trials have compared the reactogenicity and immunogenicity of the measles monovalent vaccine administered by aerosol or by injection to infants [5–10] or to school-age children [11–16]; the authors compared the monovalent vaccine with the MR, both of which were administered either by aerosol or by injection [14,15]. In most of the studies, an immune response to the aerosolized measles vaccine that was equivalent to or greater than that produced by injection was documented.