22. Prevention of infectious diseases: vaccination, chemoprophylaxis

Vaccination prevents 2-3 million deaths every year
- An additional 1.5 million deaths could be avoided with further vaccination
Immunogenicity
- = the ability of a vaccine to provoke an immune response
- Can be measured by measuring circulating antibodies
Protectivity
- = how well the vaccine protects against the disease
- Must be measured with long-term observational studies
Reactogenicity
- = how many adverse reactions the vaccine produces
Complications of vaccines
- = serious side effects
- Very rare
- Most commonly severe allergic reactions
  - Staff is trained to handle it
- The Hempt-vaccine against rabies was used until ’89, but was stopped because it caused demyelination
Accidents related to vaccination
- Misdosage
- Inappropriate administration technique
- Using expired vaccines
- Not following the correct schedule
- Using contaminated vaccines
“Ideal” vaccine
- 100% efficiency for all ages
- Only needs a single administration
- Does not cause side effects
- Stable under various environmental conditions
- Easily administrated (preferably oral)
- Low price
- Obviously doesn’t exist

Types of vaccines

Live, attenuated vaccine
- The pathogen is attenuated, meaning that it is manipulated to become much less pathogenic
- The attenuated pathogen has limited ability to reproduce in humans
- Advantages
  - The closest vaccine to a natural infection
  - Provokes both humoral and cellular immune response
  - Long-term effective protection with only one or two doses
- Disadvantages
  - Can’t be given to immune compromised patients
  - Need to be continuously refrigerated
  - Small risk of the pathogen turning virulent
  - Currently very hard to make for bacteria
- Examples
  - MMR
  - Chickenpox (varicella)
  - BCG (Tuberculosis)
  - OPV (oral polio vaccine, Sabin)
Inactivated vaccine (= killed vaccine)
- The pathogen is killed with chemicals, heat or radiation
- Advantages
  - No risk of the pathogen turning virulent (as it is dead)
  - No refrigeration needed (as it is dead)
- Disadvantages
  - Stimulates weaker immune response
  - Several doses and booster shots are necessary, requiring regular access to healthcare
- Examples
  - IPV (Salk polio vaccine)
  - HAV (Hep A)
  - Rabies
  - Influenza
Toxoid vaccine
- Can be made for bacteria who produce toxins
- Toxin is extracted from the bacterium and inactivated with formalin, so that it is no longer pathogenic -> now called a toxoid
- Used when the illness is caused by the toxin and not the bacterium itself
- Advantage
  - Rarely causes side effects
  - Stable, doesn’t require refrigeration
  - No risk of acquiring the disease
- Disadvantage
  - Several doses may be needed
  - Stimulates weak immune response
  - Do not give herd immunity
- Examples
  - Diphtheria
  - Tetanus
Subunit vaccine
- Instead of giving the entire microbe as a vaccine, certain subunits (antigens) are given instead
- Examples
  - Hepatitis B (HBsAg)
  - Acellular pertussis (aP)
Conjugate vaccine
- For bacteria protected by a polysaccharide capsule
- Polysaccharides are weak antigens, meaning that they stimulate weak immune responses
- The polysaccharide antigen of a bacterium is conjugated (attached to) a highly immunogenic protein antigen
- This stimulates a strong immune response against both the polysaccharide antigen and the protein antigen
- Advantages
  - Give a strong immune response with long-term protection
- Disadvantages
  - Multiple shots or booster shots may be necessary
- Example
  - Haemophilus influenzae type b
  - Meningococcus (Neisseria meningitidis)
RNA vaccine
- The Comirnaty (by BioNTech and Pfizer) and Spikevax (by Moderna) were the first widely available RNA vaccines, but the RNA vaccine technology has been worked on for decades
- These vaccines deliver non-replicating RNA to human host cells at the injection site. The RNA encodes the spike (S) protein from the SARS-CoV-2 virus. The host cells express this RNA, producing the spike protein, against which the immune system mounts both humoral and cellular immune responses
- The RNA vaccines are safe and effective
DNA vaccine
- Only in experimental stages
- Genes for antigens are inserted into bacteria, which produce plasmids (circular DNA) of these antigen genes
- Plasmids are inserted into the body. Cells of the body will take up the plasmids and start synthesizing the antigen from the plasmid
- The immune system recognizes the antigen produced as foreign and triggers immune response
Recombinant vector vaccines
- Only in experimental stages
- Genes for antigens are inserted into bacteria, which synthesize large amounts of the antigen
- Antigen is then purified and given as a vaccine

Who gets vaccines:

Age-specific compulsory vaccines
- BCG
- Haemophilus influenzas type b
- DTaP (diphtheria, tetanus, acellular pertussis)
- IPV (Salk polio)
- MMR (measles, mumps, rubella)
- Hepatitis B
- Pneumococcus
- HPV
Compulsory vaccines for at-risk groups
- Tetanus
- Rabies
- Hepatitis A
Non-compulsory vaccines for at-risk groups
- Influenza
Job-related vaccines
- Rabies
- Meningococcus
- Tick-borne encephalitis
Travel-related vaccines
- Yellow fever
- Cholera
- Typhoid fever
- Japanese encephalitis

Chemoprophylaxis

Definition: Administering drugs for the purpose of preventing disease or infection
Can be given
- Preexposure – before the exposure to the pathogen
- Postexposure – after the exposure to the pathogen but before symptoms develop
Examples
- Giving antiretroviral drugs to people at high risk for HIV right after being exposed to HIV
  - Like health care workers who come in contact with HIV
- Giving antimalaria drugs to people before, during and after travelling to malaria-prone areas
- Giving antibiotics to people who travel to areas where Traveller’s diarrhoea (ETEC) is common
- Giving antibiotics to people who have been exposed to bacillus anthracis
- Giving antibiotics to people who have been exposed to Neisseria meningitidis