Page 1262 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 90 Vaccines 1223

mortality in seniors, even when a senior citizen’s antibody level week in most cases, but longer durations of viral RNA detection
remains suboptimal after vaccination. If nearly everyone around are reported in semen and urine. 79,80
a senior citizen is vaccinated and protected, a susceptible senior In summer 2016, most Zika virus infections in the continental
would be much less likely to come in contact with the influenza United States were diagnosed in travelers who returned from
virus. Enhancing uptake of the annual vaccine by all children Zika virus epidemic areas in Latin America or in their sexual
and adults is thus an effective approach to improving protection contacts. However, a few cases of local transmission had occurred
of the vulnerable population of seniors. by midsummer 2016 in southern United States. These southern-
Seasonal influenza vaccine effectiveness varies year to year most parts of the country will likely experience ongoing limited
for each influenza A subtype or influenza B lineage, depending local transmissions as a result of the broad susceptibility of the
on the degree of match between the vaccine strains and the population and the presence of the primary mosquito vector
circulating strains. To allow vaccine manufacturers the 6 months Aedes aegypti. The projection for only limited local transmission
currently required for egg-based vaccine production methods, in the United States is based on recent prior experiences with
the vaccine strains for each subtype and lineage must currently dengue and chikungunya, which are also spread by the same
be selected in February for the following season’s vaccine cam- mosquito vector. However, the risk and magnitude of harm that
paign. The burden of annual revaccination of the entire popula- will occur in the United States because of this emerging virus
tion against a variable viral target is high, both logistically and is truly unknown.
financially. Furthermore, uptake of the annual seasonal influenza Although the virus was first identified nearly 70 years earlier
vaccine in the general population remains suboptimal. Over the in 1947 in the Zika forest in Uganda, only rare human infections
past decade, considerable effort has been put into the develop- had been documented in Africa and Asia for 60 years. Relatively
ment of the so-called universal influenza vaccine. The universal little scientific work was conducted. Then in 2007, a Zika virus
81
vaccine would target conserved regions on the HA protein (e.g., outbreak occurred in the Yap Islands in Micronesia, and in
82
the highly conserved stalk rather than the hypervariable head) 2013, there was an outbreak in French Polynesia. By 2015, large
or other conserved viral proteins (e.g., the M protein). Some of numbers of persons in Brazil were becoming infected, and in
the universal influenza vaccine candidates are moving into 2016, the virus continued to spread across the Americas and the
early-phase human safety and immunogenicity clinical trials. If Caribbean islands. Associations of the Zika virus with increased
a safe and effective universal influenza vaccine can be developed, incidences of microcephaly in newborns and GBS in adults led
the goal would be to replace annual revaccination against the the WHO to declare a “Global Public Health Emergency of
current season’s strains with initial vaccination and periodic International Concern” on February 1, 2016. Several governments
boosting with a universal vaccine that should protect against in the affected regions have advised women to delay pregnancy.
any influenza variant that arises each year (e.g., a booster every No vaccine or treatment is currently available.
decade as for tetanus). A further advantage would be pandemic As a response to the Zika virus epidemic, the development
preparedness and prevention because the universal influenza of a vaccine has emerged as a top priority of the US government.
vaccine, by targeting conserved viral domains present on all Preclinical work has demonstrated efficacy and human vaccine
viruses, should also protect against avian strains, such as A/ trials are on-going. A WHO website indicates that over 15
H5N1 or A/H7N9. 77,78 Finally, recent studies comparing a pharmaceutical and governmental entities are working on finding
standard-dose conventional (egg-produced) quadrivalent vaccine a Zika virus vaccine.
to a recombinant quadrivalent HA protein vaccine produced The vaccine field has a sense of optimism that a Zika virus
by a cell-line in serum-free medium demonstrated better protec- vaccine can be developed relatively quickly, given that there are
tion in older adults with the recombinant than the conventional several existing flavivirus vaccines in use around the world. The
vaccine, thus suggesting the possibility of a newer chapter in live attenuated yellow fever virus vaccine 17D, developed by
vaccine production. 78a Theiler, has been extensively used since 1927. Chimeric yellow
fever virus 17D–dengue virus vaccines have been licensed in
Zika Virus several countries, and a live attenuated dengue vaccine was recently
A current challenge that also encapsulates the recent history of shown to be protective in a human challenge study. 21,51 Further-
pathogens reemerging and spreading globally from continent more, tickborne encephalitis virus vaccines have been in use for
to continent is the ongoing Zika virus epidemic. Zika virus is a decades in Russia and Europe, and a West Nile virus vaccine
reemerging flavivirus closely related to dengue virus. As of 2015, that expresses viral antigens from a DNA vector was developed
this single-stranded positive-sense RNA virus has been causing by the NIAID and was shown to have acceptable safety and
an epidemic of mosquito-borne dengue-like illness across South promising immunogenicity in humans.
and Central Americas and the Caribbean. Infections in pregnant
women, with resulting fetal microcephaly or other birth anomalies, Other Needed Vaccines
are the most feared and serious consequences of Zika virus It is beyond the scope of this chapter to describe in detail all the
7
infection. A mosquito-borne viral cause of birth defects has new or improved vaccines that are needed to address significant
never existed before. In general, healthy adults with symptomatic infectious disease burdens. Brief mention is given to a few more
infections experience a mild to moderate self-limiting viral illness needed vaccines that have been reviewed elsewhere recently.
that has been described as “mild dengue” and is mostly character- The Ebola epidemic of 2014–2015 highlighted the importance
ized by fever, rash, conjunctivitis, and arthritis. An increased of having a vaccine ready for the next inevitable outbreak of
association of Guillain-Barré syndrome (GBS) with Zika virus that recurrent periodic killer disease. Major field trials of candidate
infection has been reported in multiple countries, and research Ebola vaccines were launched in 2015, but before the major
is ongoing to determine if a causal relationship exists. Interestingly, efficacy endpoints were achieved, the epidemic waned. However,
it is believed that 80% of Zika virus infections are asymptomatic. a preliminary result of strong efficacy for the recombinant
In symptomatic infected adults, viremia persists for less than a vesicular stomatitis virus (rVSV)–Ebola glycoprotein vaccine was