COMBINATION VACCINES :COMBINATION VACCINES DR KAUSIK SUR D.C.H,DNB ASSISTANT PFOFESSOR DEPARTMENT OF PEDIATRICS VIVEKANANDA INSTITUTE OF MEDICAL SCIENCES KOLKATA kausiksur@gmail.com


INTRODUCTION :INTRODUCTION An increasing number of new and improved vaccines to prevent childhood diseases are being introduced Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits


COMBINATION VACCINES MERGE INTO A SINGLE PRODUCT ANTIGEN THAT :COMBINATION VACCINES MERGE INTO A SINGLE PRODUCT ANTIGEN THAT Prevent different diseases (e.g. DTP) Protect against multiple strains of infectious agents causing the same disease (e.g. Poliovirus vaccines)


HISTORY :HISTORY 1945-Trivalent Influenza Vaccine 1947-Hexavalent Pneumococcal Vaccine 1948-DTP Vaccine 1955-IPV 1963-Trivalent OPV 1971-MMR 1978-Quadrivalent Meningococcal Vaccine


COMBINATION VACCINES AVAILABLE FOR MANY YEARS :COMBINATION VACCINES AVAILABLE FOR MANY YEARS DTwP MMR IPV


COMBINATIONS LICENSED IN RECENT YEARS :COMBINATIONS LICENSED IN RECENT YEARS DTwP-HiB DTwP-HeP B DTwP-IPV DTwP-IPV-HiB DTwP-HiB-HepB DTaP DTaP-IPV DTaP-HiB Hib-HepB DTaP-HepB-IPV DTaP-HiB-HepB-IPV HepA-HepB MMR-Varicella


FUTURE COMBINATION VACCINES :FUTURE COMBINATION VACCINES Increasing no. of components in different combinations to protect against these and other diseases incl. Hep A Neisseria meningitidis Streptococcus pneumoniae varicella eg. DTaP-HiB-IPV-HepB-HepA


RATIONALITY :RATIONALITY Practical way to overcome the constrains of multiple injections Improve timely vaccination coverage Reducing the cost of stocking and administering separate vaccines Reducing the cost for extra health-care visits. Facilitating the addition of new vaccines into immunization programs


BETTER ECONOMIC VALUE :BETTER ECONOMIC VALUE Direct and indirect cost of extra injections Delayed or missed vaccinations Additional handling and storage


INTERCHANGEABILITY OF VACCINE PRODUCTS :INTERCHANGEABILITY OF VACCINE PRODUCTS Interchangeability of formulations A combination vaccine can be licensed based on studies indicating that the product's immunogenicity (or efficacy) and safety are comparable with or equivalent to monovalent or combination products licensed previously A combination vaccine may be used interchangeably with monovalent formulations and other combination products with similar component antigens produced by the same manufacturer to continue the vaccination series


INTERCHANGEABILITY OF VACCINE PRODUCTS :INTERCHANGEABILITY OF VACCINE PRODUCTS Interchangeability of Vaccines From Different Manufacturers Diseases With Serologic Correlates of Immunity HEP A HEP B HiB - different Hib vaccine products from several manufacturers may be used interchangeably for sequential doses of the vaccination series A PRP-OMP HiB HbOC HiB/PRT-T HiB


Slide 12:Diseases Without Serologic Correlates of Immunity PERTUSSIS - First 3 doses - 4th and 5th dose


EXTRA DOSES OF VACCINE ANTIGENS :EXTRA DOSES OF VACCINE ANTIGENS Justified when Products that contain only the needed antigens are not readily available or would result in extra injections and Potential benefits to the child is more than the risk of adverse events associated with the extra antigens


EXTRA DOSES OF VACCINE ANTIGENS :EXTRA DOSES OF VACCINE ANTIGENS General Immunization Practice Patients commonly receive extra doses of vaccines or vaccine antigens for diseases to which they are immune Extra vaccine doses also are sometimes administered when an immunization provider is unaware that the child is already up-to-date for some or all of the antigens in a vaccine


Slide 15:Extra Doses of Combination Vaccine Antigens Live Virus Vaccines - immunity has not been demonstrated to increase the risk of adverse events eg. Varicella,MMR, Rotavirus, Poliovirus vaccines Inactivated Vaccines-Extra HiB/Hep B - Administration of extra doses of tetanus toxoid containing vaccines earlier than the recommended intervals can increase the risk of hypersensitivity reactions -Extra tetanus toxoid may be appropriate in some cases e.g. When children received DT and needed protection from Pertussis or for immigrants with uncertain immunization histories


DRAWBACKS :DRAWBACKS When different antigens are combined into one vaccine Chemical incompatibility or immunological interference Vaccine combinations requiring different schedules confusion and uncertainty Trend to develop combination products Merger of vaccine companies to acquire the needed intellectual property Reduction of competition and innovation


Slide 17:It may not always be clear which component is responsible for a particular adverse effect Research on combination vaccines is more difficult than on single antigen vaccines because they are often replacing widely used single vaccines, making trials with placebos unethical


FUTURE RESEARCH AND PRIORITIES :FUTURE RESEARCH AND PRIORITIES The interchangeability of vaccines produced by different manufacturers to prevent the same disease The safety and efficacy of administering combination vaccines to patients who might already be fully immunized for one or more of the components Economic and operations research on a) the frequency of delayed or missed vaccinations because of objections to multiple injections b) the costs of any increased disease burden caused by such missed vaccinations c) the costs of extra visits needed to comply with the routine immunization schedule d) the administrative overhead and cost of errors and confusion that might result when handling a greater number of products.


FUTURE RESEARCH :FUTURE RESEARCH The effects on immunogenicity and safety of simultaneous or repeated exposures to the same proteins used as antigens (e.g. tetanus and diphtheria toxoids) and/or as carrier components Alternative means of antigen delivery by the mucosal parenteral, and cutaneous routes, which would allow new and existing vaccines to be administered less painfully and more safely than with needles and syringes


Thank you :Thank you