The seroepidemiology of dengue in a US military population based in Puerto Rico during the early phase of the Zika pandemic.

Understanding the burden and risk factors of dengue virus (DENV) infection in Puerto Rico is important for the prevention of dengue in local, traveler and military populations. Using sera from the Department of Defense Serum Repository, we estimated the prevalence and predictors of DENV seropositivity in those who had served in Puerto Rico, stratified by birth or prior residence ("birth/residence") in dengue-endemic versus non-endemic regions. We selected sera collected in early 2015 from 500 U.

Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques.

Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. Using a heterologous prime-boost strategy in rhesus macaques, we examine the effect of priming with DENV purified inactivated vaccines (PIVs) on a tetravalent live attenuated vaccine (LAV). Sera exhibited low-level neutralizing antibodies (NAb) post PIV priming, yet moderate to high in vitro ADE activity.

Delineating the serotype-specific neutralizing antibody response to a live attenuated tetravalent dengue vaccine.

The dengue virus (DENV) vaccines that are licensed or in clinical development consist of DENV serotype 1-4 tetravalent formulations given simultaneously and are not acquired sequentially like natural infections. It is unclear what effect this has on development of protective levels of immunity to all four serotypes. Serotype-specific neutralizing antibody (NAb) is considered the most relevant correlate of protection from dengue disease.

Phenotypic analysis of dengue virus isolates associated with dengue fever and dengue hemorrhagic fever for cellular attachment, replication and interferon signaling ability.

Eighteen dengue viruses (DENVs) representing all four serotypes, isolated from pediatric patients at children's hospital, Queen Sirikit National Institute of Child Health, Bangkok, Thailand exhibiting a diverse spectrum of disease ranging from uncomplicated dengue fever (DF) to severe dengue hemorrhagic fever (DHF), were tested for their ability to attach to host cells, replicate and interfere with the IFNalpha signaling pathway by interfering with signal transducer and activator of transcription 1 (STAT-1) function. Although most isolates suppressed IFNalpha-induced STAT-1 phosphorylation, our results showed no difference between DENV strains associated with DF and those associated with DHF. However, the DHF isolates tended replicate to higher titers in dendritic cells (DCs) than the DF isolates, but this ability was independent of their cell-binding capability.

Restricted replication and lysosomal trafficking of yellow fever 17D vaccine virus in human dendritic cells.

The yellow fever virus attenuated 17D vaccine strain is a safe and effective vaccine and a valuable model system for evaluating immune responses against attenuated viral variants. This study compared the in vitro interactions of the commercially available yellow fever vaccine (YF-VAX), Dengue virus and the live-attenuated dengue vaccine PDK50 with dendritic cells (DCs), the main antigen-presenting cells at the initiation of immune responses. Similar to PDK50, infection with YF-VAX generated activated DCs; however, for YF-VAX, activation occurred with limited intracellular virus replication.

An evaluation of dengue type-2 inactivated, recombinant subunit, and live-attenuated vaccine candidates in the rhesus macaque model.

The safety, immunogenicity, and protective efficacy of two non-replicating antigen-based vaccines and one live-attenuated virus (LAV) vaccine for dengue type-2 (dengue-2) virus were evaluated in the rhesus macaque model. The non-replicating vaccines consisted of whole, purified inactivated virus (PIV) and a recombinant subunit protein containing the amino-(N)-terminal 80% of envelope protein (r80E), each formulated with one of five different adjuvants. Each formulation was administered to three animals on a 0, 3-month schedule.

Modulation of dengue virus infection of dendritic cells by Aedes aegypti saliva.

Dengue virus (DV) is a flavivirus carried by the Aedes aegypti mosquito that causes a spectrum of illnesses in the tropics, including dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Dendritic cells (DCs) are professional antigen presenting cells recently shown to be permissive for DV, and implicated as the primary targets of initial DV infection. DV is transmitted to human host by infected mosquitoes during a blood meal, but it is currently unknown whether transmission is modified by vector saliva that is also deposited in the host's skin during feeding.

A purified inactivated Japanese encephalitis virus vaccine made in Vero cells.

A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals.

Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: immunogenicity and protection in mice and rhesus monkeys.

The feasibility of a purified, inactivated dengue (DEN) vaccine made in Vero cells was explored. A DEN-2 virus candidate was chosen for production of a monotypic, purified, inactivated vaccine (PIV). Virus was harvested from roller bottle culture supernatants, concentrated, and purified on sucrose gradients.

Large-scale purification of inactivated hepatitis A virus by centrifugation in non-ionic gradients.

Formalin-inactivated hepatitis A virus (HAV) can be purified for vaccine preparation by centrifugation in Renografin-76 (diatrizoate meglumine and diatrizoate sodium) gradients. Both continuous-flow rate-zonal and isopycnic methods were used for the separation of a major antigen component from minor antigen and host protein. The major antigen component, which appeared to contain complete virions by electron microscopy, could be recovered from gradients and accounted for approximately one third of the total antigen in the starting material.

Preparation of noninfectious hepatitis A virus hemagglutinin for detecting hemagglutination inhibition antibodies.

Hepatitis A virus (HAV) harvested from infected MRC-5 cells can hemagglutinate various species of erythrocytes at acid pH (Eckels et al., 1989). Further studies revealed that the majority of the hemagglutinin (HA) in MRC-5 and BS-C-1 cells was cell-associated.