Publications by authors named "Chandrika B Kannadka"

The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • The need for next-generation SARS-CoV-2 vaccines is driven by the emergence of new variants and long-term coronavirus risks, leading to the creation of four types of engineered nanoparticle immunogens that mimic key parts of the virus.
  • These immunogens successfully stimulated strong antibody responses in mice, with one type, the Spike-ferritin nanoparticle (SpFN), producing significantly higher neutralizing antibody levels after just one shot compared to convalescent serum.
  • Immunizations with SpFN and another type, RBD-Ferritin nanoparticle (RFN), provided protection in mice against lethal SARS-CoV-2 infections and generated potent neutralizing antibodies against
View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Background: Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs.

Methods: Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities.

View Article and Find Full Text PDF

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa.

View Article and Find Full Text PDF

BAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC). Responses to intravenous injections of BAY 41-8543 were investigated under baseline and elevated tone conditions and when NO synthase (NOS) was inhibited with N(ω)-nitro-L-arginine methyl ester (L-NAME). Under baseline conditions, intravenous injections of BAY 41-8543 caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and increases in cardiac output.

View Article and Find Full Text PDF