Chapter 9. Conjugate Vaccines: Design and Development Considerations

Conjugate vaccines have proven to be a tremendous success story since their introduction more than 30 years ago. Glycoconjugate vaccines have been demonstrated not only to be effective in preventing bacterial diseases caused by Haemophilus influenzae type b (Hib) and also pneumococcal and meningococcal diseases, but also to have significant potential to curb antibiotic use to target antimicrobial resistance. By reducing the incidence of typhoid fever, the introduction of typhoid conjugate vaccine has been determined to reduce the use of antibiotics significantly. Vaccination of women during pregnancy (maternal immunization) has emerged recently as an effective prevention strategy to address infant morbidity and mortality. Although a significant majority of the success and impact of the conjugates can be attributed to glycoconjugates as commercially licensed prophylactic vaccines, small-molecule and peptide–protein conjugate vaccines also have a significant role to play in meeting the unmet need for many diseases primarily as therapeutic vaccines. The choice of the chemistry route to produce a conjugate vaccine is only the first minimal step towards the generation of an optimal conjugate construct. A ‘constellation’ of key attributes ultimately defines this optimal conjugate construct. The glycoconjugate vaccine constructs typically are a heterogeneous mixture of molecules and are rarely produced as single molecules. In other words, ‘process is the product’ essentially is the success quality mantra for glycoconjugate vaccines. Therefore, early development studies should consider several factors, such as stability, consistency of critical and key quality attributes and manufacturability during the design and development of conjugate vaccines.