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.