Active and Passive Immunity, Vaccine Types, Excipients and Licensing
Active and Passive Immunity, Vaccine Types, Excipients and Licensing
doi:10.1093/occmed/kqm110
IN-DEPTH REVIEW
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Abstract Immunity is the state of protection against infectious disease conferred either through an immune
response generated by immunization or previous infection or by other non-immunological factors.
This article reviews active and passive immunity and the differences between them: it also describes
the four different commercially available vaccine types (live attenuated, killed/inactivated, subunit
and toxoid): it also looks at how these different vaccines generate an adaptive immune response.
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Key words Active immunity; immunization; immunoglobulin preparations; passive immunity; vaccine
excipients; vaccine licensing; vaccine types.
Ó The Author 2007. Published by Oxford University Press on behalf of the Society of Occupational Medicine.
All rights reserved. For Permissions, please email: [email protected]
D. BAXTER: ACTIVE AND PASSIVE IMMUNITY, VACCINE TYPES, EXCIPIENTS AND LICENSING 553
selected from the USA. One millilitre contains not in addition, some infections, for example pertussis, ap-
,150 IU of rabies antibody. It is given as part of pear to be partly toxin mediated [3,4].
post-exposure prophylaxis to non-immune individ- In tetanus, the principal toxin (termed tetanospasmin)
uals with a rabies prone exposure. binds to specific membrane receptors located only on pre-
(iii) Human Tetanus Immunoglobulin Ph.Eur.* Bio synaptic motor nerve cells. Subsequent internalization and
Products Laboratory: Human tetanus immunoglob- migration of this toxin to the central nervous system blocks
ulin is presented as a vial size of 250 IU. Each milli- the metabolism of glycine which is essential for the normal
litre contains 40–180 mg/ml human protein of which functioning of gama amino butyric acid (GABA) neurons.
at least 95% are gammaglobulins (IgG). This prod- As GABA neurons are inhibitory for motor neurons, their
uct is prepared from plasma from screened donors, non-functioning results in excess activity in motor neurons
selected from the USA. One millilitre contains not with the muscles supplied by these nerves contracting
,100 IU of tetanus antibody. It is unlikely that this more frequently than normal giving rise to muscle spasms
preparation would be used for health care workers; it which are a characteristic feature of tetanus.
is given both as part of the management of tetanus Tetanus toxoid vaccine is manufactured by growing
prone wounds where there is heavy soil/manure con- a highly toxigenic strain of Clostridium tetani in a semi-
tamination and as part of the management of all synthetic medium: bacterial growth and subsequent lysis
wounds if the individual is thought to be non-immune. release the toxin into the supernatant and formaldehyde
(iv) Human Varicella-Zoster Immunoglobulin Ph.Eur.* treatment converts the toxin to a toxoid by altering partic-
then there is an isotype switch to IgG; in addition, a subset at the vaccine site are more common—this may be due
of B cells becomes memory cells. to the adjuvant or a type III (Arthus) reaction—the latter
The above mechanism describes the adaptive immune generally start as redness and induration at the injection
response to a protein antigen-like tetanus toxoid; such site several hours after the vaccination and resolve usually
antigens are termed T-dependent vaccines since the in- within 48–72 h. The reaction results from excess anti-
volvement of T helper cells is essential for the immune body at the site complexing with toxoid molecules and
response generated. Polysaccharide antigens in contrast activating complement by the classical pathway causing
generate a somewhat different response as will be de- an acute local inflammatory reaction.
scribed in the section on subunit vaccines.
The rationale for tetanus vaccination is thus based
Killed/inactivated vaccines
on generating antibodies against the toxoid which have
an enhanced ability to bind toxin compared with The term killed generally refers to bacterial vaccines,
the toxin receptor binding sites on nerve cells; in the whereas inactivated relates to viral vaccines [3,4]. Ty-
event of exposure to C. tetani, this large toxin:antibody phoid was one of the first killed vaccines to be produced
complex is then unable to bind to the receptor so neu- and was used among the British troops at the end of the
tralizing the toxin and preventing disease development. 19th century. Polio and hepatitis A are currently the prin-
Diphtheria and pertussis toxoid (in acellular pertussis cipal inactivated vaccines used in the UK—in many
vaccines) are two commercially available toxoid vaccines countries, whole cell pertussis vaccine continues to be
Killed/inactivated vaccines share the same advantages Simultaneously, non-phagocytosed polysaccharide mol-
as toxoid vaccines with the additional one that all the ecules pass along lymph channels to the same draining
antigens associated with infection are present and will lymph nodes where they encounter B cells, each with their
result in antibodies being produced against each of them. own unique BCR. Because the vaccine antigen consists of
Killed/inactivated vaccines have a number of disadvan- linear repeats of the same high molecular weight capsular
tages. They usually require several doses because the polysaccharide, it binds with high avidity to multiple recep-
microbes are unable to multiply in the host and so one tors on a B cell with the appropriate specificity. Such mul-
dose does not give a strong signal to the adaptive immune tivalent binding is able to activate the B cell without the need
system; approaches to overcome this include the use of for TH2 involvement, leading to the production of IgM.
several doses and giving the vaccine with an adjuvant [8]. Because, however, the TH2 is not involved, there is only
Local reactions at the vaccine site are more common— limited isotype switching so that only small amounts of
this is often due to the adjuvant. Using killed microbes for IgG are produced and few memory B cells formed. In an
vaccines is inefficient because some of the antibodies will adequately immunized individual, when Streptococcus pneu-
be produced against parts of the pathogen that play no moniae crosses mucosal barriers, specific IgM antibody in
role in causing disease. Some of the antigens contained serum will bind to the pathogen’s capsular polysaccharide
within the vaccine, particularly proteins on the surface, facilitating complement-mediated lysis. IgM is highly effec-
may actually down-regulate the body’s adaptive response— tive at activating complement; it is significantly less able to
presumably, their presence is an evolutionary development act as a neutralizing or opsonizing antibody.