1. The different types of vaccines used and their composition

2. This session includes: Identifying different types of vaccines used in the schedule How vaccine trials are undertaken prior to licensure Understanding the contraindications and side effects of each vaccine type

3. Type of vaccines (1) Change the way you think about Hull. October 2014 Passive immunisation antitoxins and immunoglobulins which provide immediate source of antibody Active immunisation Live vaccines – attenuated (weakened) organism which replicates in the host Killed/inactivated/subunit vaccines – killed micro-organisms, inactivated toxins or other subunits

4. Types of vaccine Change the way you think about Hull. October 2014 VaccineExamples ImmunoglobulinVaricella zoster IG Hep B IG, Tetanus IG Anti-toxinsDiphtheria anti-toxin Botulinum anti-toxin Inactivated/subunit vaccineDTaP/IPV/Hib Men C & Men B PPV & PCV HPV Live attenuatedMMR, Rotavirus BCG

5. Passive immunity Change the way you think about Hull. October 2014 Immunoglobulins are concentrated antibody preparations (given IM or IV) which provide immediate short-term protection against disease Given to individuals who are at high risk of experiencing severe disease or of developing serious complications from the disease – Most are given to high risk contacts of cases who were exposed during the infectious period and who are still within a window of time during which it can be effective (varies according to infection) – See immunoglobulin guidance in Green Book and PHE “Immunoglobulin: when to use” for further information https://www.gov.uk/government/publications/immunoglobulin-when-to-use https://www.gov.uk/government/publications/immunoglobulin-when-to-use They provide immediate protection but this is short-lasting (only a few weeks or months) They do not stimulate the immune system to produce any antibodies

6. Antibody Preparations Change the way you think about Hull. October 2014 Human source – pooled blood preparations from donors Human Normal Immunoglobulin (HNIG) (for contacts of Hep A, measles, polio and rubella) Varicella Zoster Immunoglobulin (VZIG) Hepatitis B Immunoglobulin (HBIG) Human Rabies Immunoglobulin (HRIG) Tetanus Immunoglobulin (TIG) – Monoclonal Palivizumab (to prevent respiratory syncytial virus (RSV) in children at high risk of disease) – Animal source Diphtheria anti-toxin (used for treatment of diphtheria - not prevention)

7. Change the way you think about Hull. October 2014 Live vaccines Attenuated strains which replicate in host attenuation means the virus or bacterium has been weakened to reduce virulence so it cannot cause disease in healthy people Act like natural infection live vaccines are the closest to actual infection and therefore elicit good, strong, long-lasting immune responses Live vaccines given routinely include….which ones?

8. Change the way you think about Hull. October 2014 Live vaccines

9. Change the way you think about Hull. October 2014 Inactivated vaccines Either: suspensions of whole intact killed organisms – e.g. whole cell pertussis, influenza, rabies, HepA Or: acellular and sub-unit vaccines – contain one or a few components of organism important in protection – e.g. acellular pertussis vaccine contains between 2-5 components of the whole cell pertussis bacteria – e.g. diphtheria toxoid – e.g. Hib polysaccharide

10. Men B Change the way you think about Hull. October 2014 Unlike other meningococcal capsular groups, the MenB polysaccharide capsule is very similar to human nerve cells. This means that vaccines based on the MenB polysaccharide are likely to be poorly immunogenic Bexsero ® developed with 4 antigens Three proteins discovered by “reverse vaccinology” Not specific to MenB (can potentially protect against other groups)

11. Change the way you think about Hull. October 2014 Inactivated vaccines

12. Change the way you think about Hull. October 2014 Conjugation Some bacteria (e.g. Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae) have an outer coating of sugar molecules (called polysaccharides) Polysaccharide coatings make it difficult for a baby or young child’s immature immune system to see and respond to the bacterium inside Polysaccharide vaccines are poorly immunogenic in children under 2 years old and do not stimulate long term immunological memory Conjugate vaccines have enabled us to effectively protect against which diseases?

13. Change the way you think about Hull. October 2014 Conjugation (CDC, 2016)

14. Combination Vaccines Change the way you think about Hull. October 2014 Many vaccines are combined to make it easier to give several vaccines at one time Combination vaccines reduce both number of clinic visits and number of injections needed Before combination vaccines are licensed, studies are carried out to ensure that: - the immune response to any of the combined antigens is just as good as the response to the individual vaccines - the rates of adverse reactions are the same as they would be if the vaccines were administered separately Which combinations are in the schedule?

15. Antigenic approach to vaccinology Change the way you think about Hull. October 2014 Weaken the virus e.g. MMR, rotavirus, influenza Inactivate the virus e.g. polio, influenza Use part(s) of the virus e.g. Hep B, HPV Use part of the bacteria e.g. DTaP Use the genome to predict part of the antigen (epitope) that is recognised by the immune system. Epitope prediction is central to reverse vaccinology e.g. MenB

16. Change the way you think about Hull. October 2014 Vaccine composition

17. 1796 Change the way you think about Hull. October 2014

18. Pre-clinical laboratory based work – often takes years Phase I – (small scale – adults) Phase II – (population specific) Phase III – (100s-1000s participants) Phase IV  vaccines – MHRA reporting Stages of Vaccine Trials

19. Change the way you think about Hull. October 2014 Contraindications and Precautions

20. Change the way you think about Hull. October 2014 Commonly reported reactions following immunisation Local Reactions Pain, swelling or redness at injection site Small nodules may form at injection site General Reactions Fever, irritability, malaise, fatigue, headache, nausea, vomiting, diarrhoea, loss of appetite Timing? Usually with 48 hrs for inactivated vaccines Varies for live vaccines E.g. MMR measles component (malaise, fever, rash) tend to occur 6 to 11 days following vaccination rubella component (pain, stiffness or swelling of joints) tend to occur in 2nd week following vaccination mumps component (parotid swelling) tend to occur in 3rd week following vaccination (although may occur up to 6 weeks following vaccination)

21. Men B Change the way you think about Hull. October 2014 Injection site reactions, fever & irritability Fever – more common when MenB given with other routine vaccines rather than given alone (≥38°) Peak at 6 hrs but gone by 48 hrs Some debate over giving paracetamol routinely post vaccination (lowers antibody response) Immunogenicity of Bexsero ® not affected by paracetamol use Advice is to give paracetamol routinely post vaccination

22. Change the way you think about Hull. October 2014 Risk of reactions versus risk of disease For all vaccine-preventable diseases, the risk of complications is much greater than risk of a serious adverse reaction following vaccination e.g. Natural measles, mumps or rubella infection versus MMR vaccine

23. Change the way you think about Hull. October 2014 Adverse events Live vaccines: frequency of adverse events falls with number of doses – Eg MMR – Because if antibody is made in response to first dose of live vaccine, it neutralises the small amount of vaccine virus in any subsequent vaccine dose Inactivated vaccines: frequency of adverse events increases with number of doses – Eg tetanus, pertussis – Because if antibody levels are good following previous vaccination, the antibody binds to the vaccine antigen in a subsequent dose of vaccine making an inflammatory response (such as a sore arm).