Vaccine 19 (2001) S87–S95 The potential for using protein vaccines to protect against otitis media caused by Streptococcus pneumoniae David E. Briles a,b, *, Susan K. Hollingshead a , Gary S. Nabors c , James C. Paton d , Alexis Brooks-Walter a a Department of Microbiology, Uniersity of Alabama at Birmingham (UAB), Birmingham, AL, USA b Department of Pediatrics, Uniersity of Alabama at Birmingham (UAB), Birmingham, AL, USA c Aentis Pasteur, Swiftwater, PA, USA d Molecular Biology Unit, Woman’s and Children’s Hospital, North Adelaide, SA, Australia Abstract Potential vaccine strategies against otitis media are to prevent (1) symptomatic infections in the middle ear and/or (2) carriage of pneumococci and thereby subsequent middle ear infections. The possibility of using immunity to virulence proteins of pneumococci to elicit immunity against pneumococci has been examined. PspA has been found to have efficacy against otitis media in animals. Vaccination with a mixture of PsaA and PspA has been observed to offer better protection against nasal carriage in mice, than vaccination with either protein alone. PspA and pneumolysin have been shown to elicit protection against invasive infections. The inclusion of a few of these proteins into the polysaccharide-protein conjugate vaccines may be able to enhance their efficacy against otitis media and might be able to constitute a successful all-protein pneumococcal vaccine. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: PspA; PsaA; Streptococcus pneumoniae www.elsevier.com/locate/vaccine 1. Introduction The reservoir of Streptococcus pneumoniae in the human population is thought to reside largely in the asymptomatic carriage of pneumococci in the nasopharynx. Under predisposing conditions, especially following infection with respiratory viruses and block- age of the estuation tube, the pneumococci colonizing the upper airways are able to cause symptomatic otitis media (Figure 1). Vaccines could protect against otitis media by protecting against infection in the middle ear, by preventing nasopharyngeal colonization of the im- munized individual, or by reduction of carriage of the population from whom at risk individuals can acquire pneumococci. For the pneumococcus the reduction of carriage would also be required for herd immunity, since it is from carriers that most pneumococci are thought to be acquired. The most successful vaccines against otitis media will probably be those that elicit herd immunity, as well as immunity to carriage and otitis. Since pneumococci also cause meningitis, bac- teremia, and respiratory infections in children, it would also be desirable for a vaccine against otitis media to protect against pneumonia and invasive disease. Otitis media is the most common infection caused by Streptococcus pneumonia in children in the developed world [1]. Another major cause of this otitis media, type b Haemophilus influenzae, has recently been brought under control in the developed world by a polysaccha- ride-protein conjugate vaccine [2]. This vaccine was prepared by covalently linking the type b polysaccha- ride to one of two different protein antigens that are highly immunogenic in children. The success of the type b conjugate vaccine has been dependent in large part on the fact that immunization with it has greatly decreased carriage of H. influenzae, with a resultant increase in herd immunity [2]. Since widespread immunization with the type b conjugate vaccine has caused type b H. influenzae to be carried at a lower frequency, the expo- * Corresponding author. Present address: BBRB 658, 1530 3rd Ave. South, Birmingham, AL 35294-2170, USA. Tel.: +1-205- 9346595; fax: +1-205-9340605. E-mail address: dbriles@uab.edu (D.E. Briles). 0264-410X/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0264-410X(00)00285-1