Page 1256 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 90 Vaccines 1217

in the United States and offers advantages, such as protein purity Year-round
(because the genes-of-interest are expressed in relative isolation) WHO surveillance and epidemiology of circulating influenza strains
and vaccine safety (because it is no longer necessary to derive Production timeline
vaccines by partially purifying the HBsAg from paid-donor plasma Feb Mar Apr May Jun Jul Aug
of humans chronically infected with hepatitis B virus and
potentially other viruses). Six months
Another example of a highly effective recombinant vaccine Feb
is the HPV vaccine. Recombinant HPV L proteins expressed in WHO announces influenza strain selections for trivalent and quadrivalent
recombinant systems form VLPs that are purified and formulated seasonal vaccines
with or without an adjuvant. The most recent polyvalent vaccine
expresses VLPs representing nine HPV serotypes. HPV vaccines Mar
are truly remarkable for their efficacy and safety and because Manufacturers obtain influenza vaccine viruses from WHO
they offer primary prevention against several types of cancer in
both females and males. Apr
It is notable that several countries have recently licensed the Cloning of recombinant viruses and adaptation for
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first dengue vaccine. It is a recombinant live viral vector that efficient egg growth
is based on the yellow fever virus vaccine strain 17D but in which May
the E and preM genes of 17D have been replaced by the E and Testing egg-grown viruses for antigenic stability;
preM genes of dengue serotypes 1, 2, 3, and 4. Four separate Expansion and growth of stocks
recombinant vectors were developed, one for each of the four June
dengue serotypes. The fact that the dengue virus and yellow Production and purification of millions of
fever virus are both flaviviruses with similar genetic organization vaccine doses
facilitated development of this chimeric yellow fever–dengue
vaccine. The final formulation is a tetravalent mixture of recom- July
binant viruses representing all four dengue serotypes. Vialing, quality control, and
potency testing
Over the last decade, systems biology, or systems vaccinology,
approaches to vaccine development have captured considerable August
interest. 52-55 The use of new high-throughput assays to assess Shipment and delivery to
multiple dimensions of innate and adaptive immune responses clinical sites
has generated very large data sets. In addition to the traditional
cellular and humoral immunological assays (antibodies, T cells, Sep – Mar
B cells), multiple “-omics” assays, including transcriptomics, Annual vaccine campaign
proteomics, metabolomics, lipidomics, and glycomics, among FIG 90.2 An Approximation of the Current Annual Influenza
others, may be performed. These detailed assessments are being Vaccine Production Process for the Northern Hemisphere.
applied in a variety of infectious and noninfectious disease states. This is the process for egg-based vaccine production. A few
One advantage for vaccine systems biology studies that enroll manufacturers’ recombinant vaccine techniques have recently
generally healthy study participants is the ability to obtain one eased the tight annual timeline, but most vaccines remain egg
or more baseline, preperturbation (prevaccination) sets of samples based. Development of a universal vaccine would obviate this
for analysis. Postvaccination changes can therefore be compared challenging and time-constrained annual process.
with the undisturbed condition. Analyses and integration of the
huge amounts of collected data require multidisciplinary col-
laboration with computational biologists and informaticians.
One application of the systems vaccine approach is to dissect vaccine once, followed by tetanus boosters every 10 years; zoster
the “-omics” responses produced by protective vaccines to identify vaccination at age 60 years; and pneumococcal vaccination at
associated changes at the RNA, protein, metabolite, lipid, and/ age 65 years. It should be noted that although the US Food and
or glycans levels. The promise, and some might say “hype,” of Drug Administration (FDA) has licensed a zoster vaccine for
systems vaccinology is both exciting and unfulfilled—and will use at age 50 years, the ACIP recommendations do not always
be realized once actual improvements in human health have align completely with FDA indications (hence the ACIP recom-
been achieved as a result of the systems approach. mendation for the zoster vaccine at age 60 years).
The adult schedule also provides recommendations for vaccines
CURRENT RECOMMENDATIONS indicated for certain risk factors, including medical conditions
(e.g., immunocompromising conditions, kidney failure, diabetes)
Currently in the United States, clear guidelines recommend or life style, occupational, or other conditions (e.g., pregnancy,
vaccines for children, adolescents, and adults. Each February, men who have sex with men, health care personnel). Live vaccines
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the CDC publishes two immunization schedules based on the (varicella, zoster, and MMR) are contraindicated in pregnant
recommendations of the CDC’s Advisory Committee on Immu- women, immunocompromised hosts, and those with human
nization Practices (ACIP). One ACIP schedule of immunizations immunodeficiency virus (HIV) infection when the CD4 T-cell
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provides the adult immunization recommendations (Fig. 90.3). absolute count is below 200 cells/µL.
The adult schedule has recommendations for each vaccine based The second ACIP immunization schedule of immunizations
on the age of the patient. For example, the ACIP recommends covers the period from birth to 18 years and includes recom-
that all adults (persons ≥19 years of age) receive annual influenza mendations for children or adolescents who have not received
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vaccination; a tetanus–diphtheria–acellular pertussis (Tdap) recommended vaccines (Fig. 90.4). The ministries of health in