Addressing a Yellow Fever Vaccine Shortage — United States, 2016–2017

Gershman, Mark D.; Angelo, Kristina M.; Ritchey, Julian; Greenberg, David; Muhammad, Riyadh D.; Brunette, Gary W.; Cetron, Martín S.; Sotir, Mark J.

doi:10.15585/mmwr.mm6617e2

Cited by 45 publications

(45 citation statements)

References 3 publications

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“…However, they are not enough to control and prevent VBD outbreaks. Despite the availability of a safe and effective yellow fever vaccine, many logistic issues with its production and distribution as well as public adherence to vaccination campaigns have impaired its effectiveness [17][18][19][20]. Recent major outbreaks in South America caused hundreds of deaths [21].…”

Section: Introductionmentioning

confidence: 99%

Cemeteries in Miami-Dade County, Florida are important areas to be targeted in mosquito management and control efforts

et al. 2020

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Definable habitats at the neighborhood level provide a wide range of favorable habitats with optimal conditions and environmental resources for mosquito survival. Problematic habitats for controlling mosquitoes in urban environments such as tire shops, bromeliad patches, and construction sites must be taken into consideration in the development of effective mosquito management and control in urban areas. Cemeteries are often located in highly urbanized areas serving as a haven for populations of vector mosquito species due to the availability of natural resources present in most cemeteries. Even though Miami-Dade County, Florida was the most affected area in the United States during the Zika virus outbreak in 2016 and is currently under a mosquito-borne illness alert after 14 confirmed locally transmitted dengue cases, the role of cemeteries in the proliferation of vector mosquitoes is unknown. Therefore, our objective was to use a cross-sectional experimental design to survey twelve cemeteries across Miami-Dade County to assess if vector mosquitoes in Miami can be found in these areas. Our results are indicating that vector mosquitoes are able to successfully exploit the resources available in the cemeteries. Culex quinquefasciatus was the most abundant species but it was neither as frequent nor present in its immature form as Aedes aegypti and Aedes albopictus. This study revealed that vector mosquitoes, such as Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus are successfully exploiting the resources available in these areas being able to thrive and reach high numbers. Mosquito control strategies should consider both long-term strategies, based on changing human behavior to reduce the availability of aquatic habitats for vector mosquitoes; as well as short-term strategies such as drilling holes or adding larvicide to the flower vases. Simple practices would greatly help improve the effectiveness of mosquito management and control in these problematic urban habitats.

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Section: Introductionmentioning

confidence: 99%

Cemeteries in Miami-Dade County, Florida are important areas to be targeted in mosquito management and control efforts

et al. 2020

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“…Stamaril ® ), an estimated ∼0.2 million YFV infections with 29,000-60,000 deaths occur annually (5). Recent YFV outbreaks in Angola (2015/16), the Democratic Republic of the Congo (2016), Brazil (2017), and Nigeria (2018), and shortage of the YF vaccine supply raised serious concerns about the preparedness for future outbreaks (6, 7). Since, the Aedes aegypti mosquito, the main YFV vector, is omnipresent in (sub)tropical Asia, YFV spill over to Asia and the establishment of epidemics involving urban transmission becomes increasingly realistic (8, 9).…”

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confidence: 99%

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

Mishra

Boudewijns

Schmid

et al. 2019

Preprint

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ABSTRACTRecent massive outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being not prepared against future YFV epidemics. Here we report that a live-attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev® that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific non-neutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV non-structural (NS) proteins. Our findings reveal the importance of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev® can confer protection against two flaviviruses. This dual protection has implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev® may already be protected against YFV should outbreaks ever occur on that continent as feared by WHO.IMPORTANCEEfficient and safe vaccines exist against yellow fever (e.g. YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses. However, vaccine supply cannot cope with an increasing demand posed by massive urban outbreaks in recent years. Here we report that JE-CVax/Imojev®, a YFV-17D-based chimeric Japanese encephalitis vaccine also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev® may be considered. Moreover, wider use of JE-CVax/Imojev® in Asia may lower the risk of the much-feared YFV spill over to the continent. More in general chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses can be considered dual vaccines, for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection [inherent to current dengue vaccines and dengue vaccine candidates] could be designed.

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“…While effective, these approaches have long development cycles and have manufacturing challenges which can restrict available vaccine supply. 2 In addition to these traditional approaches, recombinant subunit vaccines targeting the envelope (E) protein have been tested in preclinical studies and in Phase 1 clinical trials. We have previously described a novel WNV vaccine formulation containing a recombinant E-protein combined with a TLR agonist adjuvant.…”

Section: Introductionmentioning

confidence: 99%

A combination of TLR-4 agonist and saponin adjuvants increases antibody diversity and protective efficacy of a recombinant West Nile Virus antigen

Hoeven

Wiley²,

Gage

et al. 2018

npj Vaccines

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Members of the Flaviviridae family are the leading causes of mosquito-borne viral disease worldwide. While dengue virus is the most prevalent, the recent Zika virus outbreak in the Americas triggered a WHO public health emergency, and yellow fever and West Nile viruses (WNV) continue to cause regional epidemics. Given the sporadic nature of flaviviral epidemics both temporally and geographically, there is an urgent need for vaccines that can rapidly provide effective immunity. Protection from flaviviral infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. TLR agonist adjuvants represent a promising tool to enhance the protective capacity of flavivirus vaccines through dose and dosage reduction and broadening of antiviral antibody responses. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) using a novel combination adjuvant, which contains a potent TLR-4 agonist and the saponin QS21 in a liposomal formulation (SLA-LSQ). Here, we show that, in combination with WN-80E, optimized SLA-LSQ is capable of inducing long-lasting immune responses in preclinical models that provide sterilizing protection from WNV challenge, reducing viral titers following WNV challenge to undetectable levels in Syrian hamsters. We have investigated potential mechanisms of action by examining the antibody repertoire generated post-immunization. SLA-LSQ induced a more diverse antibody response to WNV recombinant E-protein antigen than less protective adjuvants. Collectively, these studies identify an adjuvant formulation that enhances the protective capacity of recombinant flavivirus vaccines.

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Addressing a Yellow Fever Vaccine Shortage — United States, 2016–2017

Cited by 45 publications

References 3 publications

Cemeteries in Miami-Dade County, Florida are important areas to be targeted in mosquito management and control efforts

Cemeteries in Miami-Dade County, Florida are important areas to be targeted in mosquito management and control efforts

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

A combination of TLR-4 agonist and saponin adjuvants increases antibody diversity and protective efficacy of a recombinant West Nile Virus antigen

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