Adjuvanted vaccine;

Dead vaccine in which pathogens or antigen components are bound to adsorbents/adjuvants (e.g. to aluminium hydroxide, aluminium phosphate or calcium phosphate). are bound. This causes, among other things, a depot effect. The antigen is released continuously over a longer period of time. Many adjuvants also increase the effectiveness of active immunisation. In principle, adjuvants do not represent a drug, but are to be regarded as a pharmaceutical adjuvant.

The following adjuvants have proven to be effective:

• Aluminium compounds: aluminium hydroxide, aluminium phosphate, aluminium hydroxyphosphate sulphate, aluminium potassium sulphate (still the most commonly used adjuvants).
• AS01: Combined adjuvant of liposomes, MPL and QS21.
• AS02: Combined adjuvant in the form of an oil-in-water emulsion consisting of MPL and QS21.
• AS03: Combined adjuvant in the form of an oil-in-water emulsion consisting of squalene, polysorbate 80, DL-α-tocopherol.
• AS04: Combined adjuvant of MPL and aluminum hydroxide or aluminum phosphate.
• CpG oligonucleotide: Immunostimulatory DNA sequences (ISS) of synthetically prepared oligonucleotides with CpG motifs.
• IC31: Combination of the peptide KLK with the oligodeoxynucleotide ODN1.
• ISCOM: ISCOM is the acronym for "immunostimulatory complexes". Immunostimulatory complexes contain phospolipids and cholesterol as well as purified extracts of quillaja saponins derived from the bark of the soap bark tree.
• ISCOMATRIX: Consists of purified quillariasaponin QS21, cholesterol and phospholipids of the cell membrane, which form 40-50 nm "cage structures" under suitable conditions.
• MF59: Oil-in-water emulsion containing squalene, polysorbate 80, sorbitan trioleate (Span 85), sodium citrate and citric acid.
• MPL: Monophosphoryl lipid A, a purified derivative of lipopolysaccharides from bacterial cell walls of Salmonella minnesota.ingredient of combined adjuvants (AS0x).
• QS-2: Surface active substance(saponin) from the bark of the South American soap bark tree(Quillaja saponaria). Used as a matrix in the so-called ISCOMs (immunostimulating complexes) and in the combined adjuvants.
• Virosomes: double membrane of phospholipids (liposomes) into which the viral antigen structures (e.g. influenza virus A haemagglutinin and neuraminidase) are incorporated; they act like a reconstituted ("artificial") viral envelope.

In the case of adsorbate vaccines, care should be taken to ensure that they are injected intramuscularly. Subcutaneous application can lead to painful, granulomatous reactions at the injection site.

One possible reason for a stronger local reaction of an adsorbate vaccine is an injection needle wetted with the vaccine. This makes the injection painful and can lead to inflammation in the area of the injection canal. The STIKO points out that the injection needles must always be "dry" during vaccinations, i.e. no vaccine should wet the outside of the needle. After drawing the vaccine into the syringe and removing any air that may be present, a new needle should therefore be fitted for the injection. Incidentally, the small amount of air present in the cannula itself can be disregarded. This also applies to pre-filled syringes. Thus, one should refrain from injecting the air in a cannula (Hof H et al. 2019).

The rule applies that the smaller the antigenic molecule in question, the more the adjuvant is needed to achieve the desired immune-enhancing effect. This rule does not apply to live vaccines and vaccines from whole bacterial germs, as these do not require adjuvants to achieve an appropriate immune response. The following adjuvants are commonly used in adsorbed vaccines, with aluminium compounds being the most important.

1. Einstein MH et al. (2014) HPV-010 Study Group. Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18AS04-adjuvanted
   vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: end-of-study analysis of a phase III randomized trial. Hum VaccinImmunother
   10:3435-3445.
2. Gellin BG et al (2015) Communicating the role and value of vaccine adjuvants
   . Vaccine 33 Suppl 2:B44-6.
3. Hof H et al (2019). Active immunization. In: Hof H, Schlüter D, Dörries R, eds Dual series medical microbiology. 7th, completely revised and expanded edition. Stuttgart: Thieme p 739-742