A vaccine dose contains many ingredients (such as stabilizers, adjuvants, residual inactivating ingredients, residual cell culture materials, residual antibiotics and preservatives) very little of which is the active ingredient, the immunogen. A single dose may have merely nanograms of virus particles, or micrograms of bacterial polysaccharides. A vaccine injection, oral drops or nasal spray is mostly water. Other ingredients are added to boost the immune response, to ensure safety or help with storage, and a tiny amount of material is left-over from the manufacturing process. Very rarely, these materials can cause an allergic reaction in people who are very sensitive to them.
Volume
The volume of a vaccine dose is influenced by the route of administration. While some vaccines are given orally or nasally, most require an injection. Vaccines are not injected intravenously into the bloodstream. Most injections deposit a small dose into a muscle, but some are given superficially just under the skin surface or deeper beneath the skin. Fluenz Tetra, a live flu vaccine for children, is administered nasally with 0.1ml of liquid sprayed into each nostril. The live typhoid vaccine, Vivotif, and a live adenovirus vaccine, licensed only for military use, both come as hard gastro-resistant tablets. The Sabin oral live polio vaccine is taken as two 0.05ml drops of a bitter salty liquid that was historically added to sugar cubes when given to young children. Rotarix, a live rotavirus vaccine, has about 1.5ml of liquid containing 1g of sugar to make it taste better. The Dukoral cholera vaccine comes as a 3ml suspension along with 5.6g of effervescent granules, which are mixed and added to around 150ml water to make a sweet raspberry flavoured drink. At the other end of the volume scale, the smallpox vaccine is a minuscule 0.0025ml droplet that is picked up when a bifurcated needle is dipped into a vial containing around 100 doses. This needle is pricked 15 times into a small area of skin, just firmly enough to produce a drop of blood. A little larger is the BCG tuberculosis vaccine, which is 0.05ml for babies and children under 12, and 0.1ml for others. This tiny dose is inserted a couple of millimetres under the skin, producing a small blanched blister. Many vaccines for intramuscular injection have 0.5ml liquid, though a few have 1ml. Some vaccines come with the active ingredients already suspended in solution and the syringe pre-filled (e.g., Bexsero meningococcal Group B vaccine). Others are supplied as a vial of freeze-dried powder, which is reconstituted prior to administration using a dilutant from a separate vial or pre-filled syringe (e.g., MMR vaccine). Infanrix hexa, the 6-in-1 vaccine that protects against six diseases, uses a combination approach: the Hib vaccine in the powder and DTPa-HBV-IPV in suspension. Alternatively two separate vaccine solutions are mixed just before administration (ViATIM hepatitis A and typhoid vaccine).
Immunogens Many vaccines developed in the 20th century contain whole bacteria or viruses, which are either inactivated (killed), attenuated (weakened) or a strain chosen to be harmless in humans. Since these are so small, even a tiny amount of them contains a huge number of individuals. With bacterial vaccines, we can enumerate this with an approximate number of bacteria cells. The live typhoid vaccine contains two billion viable cells of Salmonella enterica subsp. enterica serovar Typhi, which have been attenuated and cannot cause disease. The cholera vaccine has over thirty billion of each of four strains of Vibrio cholerae, which are inactivated by heat or formalin. The BCG vaccine, infant dose, contains between 100,000 and 400,000 colony-forming unit of live attenuated Mycobacterium bovis. One way to count viruses is to observe their impact on host cells in tissue cultures. The two tablets of adenovirus vaccine, one with adenovirus type 4 and the other with type 7, each contain 32,000 tissue-culture infective doses (104.5 TCID50). The current live polio vaccine contains two serotypes of poliovirus: over 1 million tissue-culture infective doses (106 TCID50) of type 1 and over 630,000 (105.8 TCID50) of type 3. The smallpox vaccine contains between 250,000 and 1,250,000 plaque forming units of live vaccinia virus per dose. The MMR vaccine contains 1,000 TCID50 measles, 12,500 TCID50 mumps and 1,000 TCID50 rubella live attenuated viruses. Many modern vaccines are made of only the parts of the pathogen necessary to invoke an immune response (a subunit vaccine) – for example just the surface proteins of the virus, or only the polysaccharide coating of a bacterium. Some vaccines invoke an immune response against the toxin produced by bacteria, rather than the bacteria itself. These toxoid vaccines are used against tetanus, diphtheria and pertussis (whooping cough). If the bacteria polysaccharide coating produces only a weak immune response on its own, it may be combined with (carried on) a protein that does provoke a strong response, which in turn improves the response to the weaker component. Such conjugate vaccines, may make use of a toxoid as the carrier protein. For all these, the quantity of immunogen is given by weight and sometimes expressed as international units (IU). The HVP vaccine contains 120 micrograms of the L1 capsid proteins from four types of human papillomavirus. The pneumococcal conjugate vaccine contains 32 micrograms of pneumococcal polysaccharide conjugated with CRM197 (a diphtheria toxin). Another variant is the RNA vaccine, which contains mRNA embedded in lipid (fat) nanoparticles. The mRNA instructs body's own cell machinery to produce the proteins that stimulate the immune response. Comirnaty, the Pfizer-BioNTech COVID-19 vaccine contains thirty micrograms of BNT162b2 RNA.
Excipients
Excipients are substances present in the vaccine that are not the principal immunological agents. These may be present to enhance the vaccine's potency, ensure safety, aid with storage or are left over from the manufacturing process.
Adjuvants
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