MICR2221 vaccines

adjuvant

component of vaccine that promotes or amplifies adaptive immune response

act directly or indirectly to promote DC activation (req for naive t cell activation) or other aspects of response

do some vaccines have inherent adjuvant properties

yes, e.g. attenuated vaccines do (subunit vaccines have limited adjuvant properties)

alum adjuvants

activates the inflammasome

causes neutrophil infiltration and DAMP release

increase DC migration to lymph nodes

ppt. of aluminium hydroxyphosphate

good at promoting humoral but bad at cell mediated immunity

MF59

oil in water (squalene)

induces monocyte recruitment to injection site and DAMP release

increase DC migration to lymph nodes

GSK adjuvant system 04 (AS04)

alum with monophosphoryl lipid A (MPLA)

MPLA is an endotoxin like mol that stim TLR4

(less toxic than LPS)

increases co stim mol exp

does route of administration affect immune response

yes, IM gets IgG response mainly, e.g. bad for mucosal sites where IgA mostly

live attenuated vaccines

attenuation diminishes virulence of pathogen while retain antigens that promote immune response

performed by passing virus thru cell culture, that intro muts that decrease virulence to humans

singif adjuvant properities

can revert to virulent form

~Sabin Oral Polio vaccine

live attenuated, cont. 3 polio strains

10 muts of 7429 nt. difference

transiently infects the host, stim IgA prodution in gut

inactivated (killed vaccine)

unable to divide

cant revert back to virulent form

used in immunodeficient too

dont persist as long as attenuated plus less stimuating

Salk inactivated polio vaccine

3 diff polio virus strains

inactivated with formaldehyde

IM

so less mucosal immunity than Sabin oral vaccine

cant revert to virulent strain

subunit vaccines

contain part of pathogen

proteins, inactivated toxins (toxoids), non protein antigens

bi as immunogenic

ghow

how can limited imunogenicity of a vaccine be overcome

multiple doses to increase period of stimulation

use adjuvants

HPV vaccine

against strains 6,11,16,18 linked to cervical cancer

use L1 capsid proteins of these types that prod virus like particles

alum adjuvant

non infectious as no nucleic acid, but promote ab mediated response

are toxoids immunogenic by themselves

no req adjuvant (to activate DC cells)

conjugate vaccines

conjugate non protein, pathogen assoc mols to proteins (toxoids)

as T cells dont recognise non proteins normally, so can get t cell activation to toxoid for b cells specific to e.g. capsular polysaccharides