15.2 Using Amphipols to Formulate a Subunit Vaccine Against
Chlamydia trachomatis
In the following, we will briefly consider the results of attempts at using APols to improve the
efficiency of a vaccine against the intracellular pathogenic bacterium Chlamydia trachomatis, before
listing a few suggestions about how APols could contribute, more generally, to improving the
formulation of vaccines. As will be discussed in the conclusion, the exploitation of APols in this
area of medical research has been much neglected given its prospects, for reasons that, in my view, are
more cultural than factual.
15.2.1 Background
Historically, vaccines have been prepared using whole pathogenic microorganisms that have been
rendered harmless by either “attenuating” or killing them. Attenuation is achieved by repeatedly
growing the organism in a foreign host, until it loses its virulence to humans. Killing is achieved by
treating the organisms with chemicals, heat, or radiation. For a number of reasons, these vaccines
tend to be the most efficient, but they cannot always be produced, viz. the cases of HIV, malaria,
tuberculosis in adults, Staphylococcus aureus, or the dengue virus (for recent reviews, see e.g. Levine
et al. 2010; Delany et al. 2014; Doolan et al. 2015; Plotkin et al. 2017). Furthermore, they do have their
problems, such as safety and storage issues with attenuated pathogens. Vaccines based on whole
organisms present a risk of batch-to-batch variations, and subjects are injected with a host of ill-defined
molecules besides the desirable immunogens, some of which can cause side effects, such as hypersensitivity reactions. This has led to the development of alternative approaches, among which are
recombinant DNA-based vaccines and “subunit” vaccines, in which purified immunogens can be
injected either free or attached to a carrier (for recent reviews, see e.g. Moyle and Toth 2013; Bobbala
and Hook 2016; Vartak and Sucheck 2016).
In the context of vaccine formulation, the term “subunit” does not refer to a protein that is part of
an oligomer, as it does in biochemistry, but to an immunogen comprising subcellular elements that
have been extracted from the pathogenic organism or synthesized, rather than whole cells or viral
particles. These elements can be proteins, nucleic acids, lipids, polysaccharides, subcellular fragments,
inactivated toxins (toxoids), etc. The use of highly purified molecules strongly improves, if not
eliminates, the safety risk associated with biologics production. Subunit vaccines are generally easier
to standardize and to store than those based on attenuated or killed pathogens, which improves product
consistency, but they are also much less immunogenic (Moyle and Toth 2013; Bobbala and Hook
2016). Approaches to increasing their immunogenicity include binding them to a carrier, with the risk
of potential batch-to-batch variations, and co-injecting them along with agents that will stimulate the
immune response (adjuvants). “Adjuvant” is a broad term that can refer either to a chemical that will
stimulate the immune response, e.g. a bacterial lipid or an oligodeoxynucleotide (ODN) mimicking
bacterial DNA, or a physical support that improves the presentation of the immunogen to the organism,
such as aluminum salts or an oil/water emulsion.
Purified membrane proteins (MPs) are not typically used in subunit vaccines, because of their
well-deserved reputation of being difficult to produce and unstable in detergent solutions (cf. Chap. 2).
APols could be game changers, for several reasons: (i) APols can facilitate large-scale production of
MPs, e.g. by helping to fold them from inclusion bodies (Chap. 6); (ii) they stabilize MPs (Chap. 5,
§ 5.5); (iii) the physical-chemical properties of APols can be modulated, which, as will be discussed in
§ 15.2.3, could play an important role in optimizing the presentation of APol-trapped MPs to the
15.2 Using Amphipols to Formulate a Subunit Vaccine Against Chlamydia trachomatis
661
Chlamydia trachomatis
In the following, we will briefly consider the results of attempts at using APols to improve the
efficiency of a vaccine against the intracellular pathogenic bacterium Chlamydia trachomatis, before
listing a few suggestions about how APols could contribute, more generally, to improving the
formulation of vaccines. As will be discussed in the conclusion, the exploitation of APols in this
area of medical research has been much neglected given its prospects, for reasons that, in my view, are
more cultural than factual.
15.2.1 Background
Historically, vaccines have been prepared using whole pathogenic microorganisms that have been
rendered harmless by either “attenuating” or killing them. Attenuation is achieved by repeatedly
growing the organism in a foreign host, until it loses its virulence to humans. Killing is achieved by
treating the organisms with chemicals, heat, or radiation. For a number of reasons, these vaccines
tend to be the most efficient, but they cannot always be produced, viz. the cases of HIV, malaria,
tuberculosis in adults, Staphylococcus aureus, or the dengue virus (for recent reviews, see e.g. Levine
et al. 2010; Delany et al. 2014; Doolan et al. 2015; Plotkin et al. 2017). Furthermore, they do have their
problems, such as safety and storage issues with attenuated pathogens. Vaccines based on whole
organisms present a risk of batch-to-batch variations, and subjects are injected with a host of ill-defined
molecules besides the desirable immunogens, some of which can cause side effects, such as hypersensitivity reactions. This has led to the development of alternative approaches, among which are
recombinant DNA-based vaccines and “subunit” vaccines, in which purified immunogens can be
injected either free or attached to a carrier (for recent reviews, see e.g. Moyle and Toth 2013; Bobbala
and Hook 2016; Vartak and Sucheck 2016).
In the context of vaccine formulation, the term “subunit” does not refer to a protein that is part of
an oligomer, as it does in biochemistry, but to an immunogen comprising subcellular elements that
have been extracted from the pathogenic organism or synthesized, rather than whole cells or viral
particles. These elements can be proteins, nucleic acids, lipids, polysaccharides, subcellular fragments,
inactivated toxins (toxoids), etc. The use of highly purified molecules strongly improves, if not
eliminates, the safety risk associated with biologics production. Subunit vaccines are generally easier
to standardize and to store than those based on attenuated or killed pathogens, which improves product
consistency, but they are also much less immunogenic (Moyle and Toth 2013; Bobbala and Hook
2016). Approaches to increasing their immunogenicity include binding them to a carrier, with the risk
of potential batch-to-batch variations, and co-injecting them along with agents that will stimulate the
immune response (adjuvants). “Adjuvant” is a broad term that can refer either to a chemical that will
stimulate the immune response, e.g. a bacterial lipid or an oligodeoxynucleotide (ODN) mimicking
bacterial DNA, or a physical support that improves the presentation of the immunogen to the organism,
such as aluminum salts or an oil/water emulsion.
Purified membrane proteins (MPs) are not typically used in subunit vaccines, because of their
well-deserved reputation of being difficult to produce and unstable in detergent solutions (cf. Chap. 2).
APols could be game changers, for several reasons: (i) APols can facilitate large-scale production of
MPs, e.g. by helping to fold them from inclusion bodies (Chap. 6); (ii) they stabilize MPs (Chap. 5,
§ 5.5); (iii) the physical-chemical properties of APols can be modulated, which, as will be discussed in
§ 15.2.3, could play an important role in optimizing the presentation of APol-trapped MPs to the
15.2 Using Amphipols to Formulate a Subunit Vaccine Against Chlamydia trachomatis
661