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A review.Vaccines are well-established medical interventions capable of preventing infectious disease.There are many notable vaccine success stories, starting more than 200 years ago with the earliest work by Jenner that led to a cowpox-bascd immunization to prevent smallpox disease.Subsequent work by Pasteur during the 19th century refined and consolidated the basis of vaccinol. through the principles of isolation, inactivation, and administration of key components from disease-causing pathogens.Relatively soon, this basis had enabled the development of several "first generation" vaccines that afforded protection against rabies, typhoid, cholera, and plague (within the 19th century), followed by tuberculosis, yellow fever, and pertussis by the first half of the 20th century.Breakthroughs in mammalian cell culture technol. in the second half of the 20th century led to the development of "second generation" vaccines, protecting against polio, measles, rubella mumps, and varicella (as reviewed previously1).In the late 20th century the first polysaccharide and glycoconjugate vaccines were developed, some of which have been refined and are implemented on a global scale.

Glycoconjugate vaccines have played an enormous role in preventing infectious diseases over the past 30 years.They are composed of the purified capsular polysaccharide of a pathogenic bacterium covalently linked to a carrier protein, which enhances the immunogenicity of the carbohydrate moiety.Few carrier proteins have been tested so far for the clin. evaluation of conjugate vaccines and only five of them (DT, TT, CRM197, OMPC and NTHi protein D) are currently used for licensed vaccines against bacterial infections.Current pediatric immunization schedules include multivalent vaccines combinations and vaccines coadministration increasing the concern that repeated exposure to the same or antigenic related carriers might interfere with the anti-polysaccharide response.The impact of the immune interference, such as carrier-specific enhancement of T-cell help, carrier-induced epitopic suppression (CIES) or bystander interference might be avoided or reduced by using novel carrier proteins.In last years, alternative proteins have been evaluated as carrier and their development, which might also provide protection against a target pathogen, has been recently broadened to include candidates from diverse vaccine categories.In this framework, the use of site selective chemistries to preserve the protein antigens has been explored.A large number of recombinant proteins, derived from different bacteria, have been conjugated to the β-glucan based non charged Laminarin and the polyanionic meningococcal oligosaccharides, and their ability in inducing antibodies against the carbohydrate has been tested in the murine model.Based on immunol. data, a panel of proteins that deserve further attention has been identified; in particular, the spr96/2021 is a new potential protein carrier for carbohydrate haptens which might also offer pathogen-protective effect.6 This strategy might have an important impact to develop a new concept of vaccines that combines protein antigens selected by reverse vaccinol. with capsular polysaccharides to create vaccines with broader coverage.