Vaccine 20 (2002) 2790–2795 A randomized trial demonstrating successful boosting responses following simultaneous aerosols of measles and rubella (MR) vaccines in school age children Jaime Sepúlveda-Amor a , José Luis Valdespino-Gómez a,∗ , Ma de Lourdes Garc´ ıa-Garc´ ıa a , John Bennett b , Roc´ ıo Islas-Romero a , Gabriela Echaniz-Aviles a , Jorge Fernandez de Castro a a National Institute of Public Health, Instituto Nacional de Salud Pública/Escuela de Salud Pública de México, Ave. Universidad 655, CP62508 Cuernavaca, Mor., Mexico b Emory University, Atlanta, GA 30322, USA Received 1 October 2001; received in revised form 27 February 2002; accepted 11 March 2002 Abstract The reactogenicity and immunogenicity of combined measles and rubella (MR) booster vaccination, via aerosol and subcutaneous routes, was assessed in 562 healthy children. Rates of rubella seroconversion and geometric mean titers (GMT) were similar for both routes. Rates of measles PN seroconversion, GMT and measles ELISA post-vaccination seropositivity and seroconversion rate were each higher for aerosol vaccine (54%, 3928 IU/l, 99.6 and 98.8%), than for subcutaneous vaccine (7%, 866 IU/l, 92.2 and 82.4%) (P< 0.01). Reactogenicity was higher for subcutaneous vaccine (P< 0.05). This study demonstrates that aerosol vaccine was more immunogenic for measles antibodies, and equally immunogenic for rubella antibodies. Aerosol vaccine was less reactogenic. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: Measles; Rubella; Aerosol administration 1. Introduction Aerosol administration of measles vaccines in mass cam- paigns was first proposed by Dr. Albert Sabin [1]. Factors favoring the aerosol route include its non-invasiveness, doc- umented immunogenicity in seronegative and seropositive children, potential to stimulate local respiratory tract immu- nity and prevent reinfection, better acceptance by the popu- lation as it does not require parental injection, reduction in the risks of cross-infection entailed by parental application, lower cost, and easy administration by non-medical person- nel [2]. Aerosol administration of measles vaccine has been used in mass campaigns in Mexico, being administered both as primary and booster dose to nearly 4 million children, with fewer side effects reported than those usually observed after subcutaneous vaccination [3]. Recently, studies have shown that aerosol administration of Edmonston–Zagreb (EZ) measles vaccine is more immunogenic than subcuta- neous administration of this same vaccine or of Schwarz measles vaccine at 1 month and 1 year after vaccination [4]. ∗ Corresponding author. Tel.: +527-311-2218; fax: +527-317-5529. E-mail address: jvaldesp@insp3.insp.mx (J.L. Valdespino-G´ omez). Antibody titers continued to be substantially higher for the aerosol group at 2 years after vaccination [5]. Immunogenicity of rubella vaccine by aerosol has been demonstrated by Ganguly et al. [6,7]. Its combined admin- istration with measles vaccine intranasally has proved to be immunogenic in small-scale studies [8]. The advantages of mass campaigns with combined vaccine include the possi- bility of increasing population immunity to measles, while simultaneously achieving primary vaccination for rubella in many children in developing countries where neither measles and rubella (MR) nor MMR vaccines are routinely given. Indeed, the combination of MR vaccines in campaigns targeted towards measles elimination/eradication has previ- ously been endorsed [9,10]. Although most immunization programs in developed countries, and in some developing countries, are using combined vaccines (measles, mumps, rubella), both for primary and for booster doses [11], the addition of mumps vaccine adds considerably to the cost of MR vaccine [12], thus making MMR less attractive for mass campaigns in many developing countries. In the present study, we describe the results of a random- ized controlled study in which we compare the immuno- genicity and frequency of clinical symptomatology after 0264-410X/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0264-410X(02)00179-2