M T De Magistris

Acellular pertussis vaccines containing genetically detoxified pertussis toxin induce long-lasting humoral and cellular responses in adults

New generation pertussis vaccines, containing only purified Bordetella pertussis antigens, have been proven safe, immunogenic and efficacious. They have, however, raised new questions regarding the mechanism of protection from whooping cough and the duration of the immune response following vaccination. In addition to the antibody (Ab) titer, the level of pertussis toxin (PT) neutralizing antibodies may be very important in protection and the role of cell-ediated immunity needs to be defined. We have previously reported the safety and immunogenicity results of two phase I trials in adult volunteers with two acellular pertussis vaccines containing genetically detoxified PT alone or in combination with filamentous hemagglutinin (FHA) and 69K protein. In this work, we present the results of a long term follow-up study of the immune response in the same vaccinees. We evaluated the Ab response, the PT neutralizing titer and the peripheral blood T cell response up to 4 years following vaccination. Our results show that in adults the level of antibodies to PT, FHA and 69K and the PT neutralizing titers slightly decline between 2.5 and 12 months after the last vaccine dose, but they remain high in the following 2-4 years, showing levels 10-100 times higher than pre-vaccination values. The T cell responses were more heterogeneous among vaccinees but they did not show any significant decline throughout the period monitored.

Rational Design of Vaccine Molecules to Prevent Pertussis

Formaldehyde treatment is a process widely used in vaccine preparation to inactivate bacterial toxins such as diphtheria and tetanus (Rappuoli, 1990). Formaldehyde-inactivated bacterial toxins have been proven to be efficacious as vaccines; however, the chemical modification of a protein can affect its immunogenicity by altering B and T cell epitopes. A more rational approach for bacterial toxin inactivation is the use of recombinant DNA technology. The advantages of this approach are:i) maintainance of the native protein conformation and therefore of the original epitopes; ii) no risk of reversion to toxicity; iii) consistency in vaccine production. We therefore used this approach for the development of a new vaccine against pertussis.