MULTIVALENT VACCINE COMPOSITION

The present invention relates to stable, immunogenic combination vaccine(s) comprising a mixture of antigens for prevention and prophylaxis of infections caused by Rotavirus, Poliomyelitis virus, Haemophilus influenzae, Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis and Hepatitis B virus. The invention particularly provides a multivalent combination vaccine comprising of i) significantly dose reduced Salk IPV or Sabin IPV (IPV) antigens prepared by utilizing improved methods of formaldehyde inactivation and alum hydroxide adsorption resulting in maximum recovery of D-antigen and ii) Injectable heat inactivated Rotavirus antigen(s) obtained from Rotavirus (CDC-9) strains that provides a broad cross-protective immunity among human rotavirus strains, iii) Hib PRP -carrier protein conjugate having improved stability and immunogenicity wherein said Hib PRP -earner protein conjugate is initially prepared by using novel conjugation process and subsequently blended at low temperature in presence of a stabilizer for minimizing free PRP release iv) whole ceil pertussis antigen with improved immunogenicity and stability obtained by addition of whole cell pertussis antigen at a later stage in a blend thereby minimizing hydrolysis based degradation v) Homogenous fractions of Diphtheria toxoid and Tetanus toxoid obtained by removal of undesirable aggregates by using Gel Permeation chromatography. The process of making such stable and immunogenic vaccine compositions by i) individually adsorbing dose reduced IPV. IRV antigens on alum hydroxide and keeping other antigen(s) unadsorbed or adsorbed on Alum Phosphate, Alum hydroxide, on a combination of Alum hydroxide and Alum phosphate and ii) using a particular order of addition of antigens during blending is also disclosed. La presente invención se refiere a una vacuna o vacunas de combinación inmunogénica estables que comprenden una mezcla de antígenos para la prevención y profilaxis de infecciones causadas por el rotavirus, el virus de la poliomielitis, Haemophilus influenzae, Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis y el virus de la Hepatitis B. La invención proporciona en particular una vacuna de combinación multivalente que comprende: i) antígenos de IPV Salk o IPV Sabin (IPV) en dosis significativamente reducida, preparados mediante el uso de métodos mejorados de inactivación de formaldehído y adsorción de hidróxido de aluminio, que dan como resultado la recuperació