Moi, M. L. | Search bioRxiv

bioRxiv2024

Genomic sequencing and neutralizing serological profiles during acute dengue infection: A 2017 cohort study in Nepal

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to nearly 50% of the global population. DENV has been endemic in Nepal since 2006; however, little is known about how DENV is evolving or the prevalence of anti-DENV immunity within the Nepalese population. To begin to address these gaps, we performed a serologic and genetic study of 49 patients from across Nepal who presented at central hospitals during the 2017 dengue season with suspected DENV infection. Of the 49 subjects assessed, 21 (43%) were positive for DENV NS1 antigen; of these; 5 were also anti-DENV IgM+ IgG+; 7 were DENV IgM+ IgG-, 2 were IgM- IgG+, and 7 were IgM- IgG- by specific ELISAs. Seven of the 21 NS1+ sera were RNA+ by RT-PCR (six DENV2, one DENV3), suggesting that DENV2 was the dominant serotype in our cohort. Whole-genome sequencing of two DENV2 isolates showed similarity with strains circulating in Singapore in 2016, and the envelope genes were also similar to strains circulating in India in 2017. DENV-neutralizing antibodies (nAbs) were present in 31 of 47 sera tested (66%); among these, 20, 24, 26, and 12 sera contained nAbs against DENV1, 2, 3, and 4 serotypes, respectively. Serology analysis suggested that 12 (26%) and 19 (40%) of the 49 subjects were experiencing primary and secondary DENV infections, respectively. Collectively, our results provide evidence for current and/or past exposure to multiple DENV serotypes in our cohort, and the RNA analyses further indicate that DENV2 was the likely dominant serotype circulating in Nepal in 2017. These data suggest that expanded local surveillance of circulating DENV genotypes and population immunity will be important to effectively manage and mitigate future dengue outbreaks in Nepal.

genomics↗

bioRxiv2023

A Tetravalent Dengue Virus-like Particle Vaccine Induces High levels of Neutralizing Antibodies and Inhibits Dengue Replication in Non-Human Primates

Dengue virus (DENV) represents a significant global health burden, with 50% of the worlds population at risk of infection, and there is an urgent need for next-generation vaccines. Virus-like particle (VLP)-based vaccines, which mimic the antigenic structure of the authentic virus but lack the viral genome, are an attractive approach. Here we describe a dengue VLP (DENVLP) vaccine which generates a robust and long-lasting neutralizing antibody response against all four DENV serotypes in non-human primates. Importantly, DENVLP vaccination produced no ADE response against any of four DENV serotypes. Finally, we demonstrate in a non-human primate challenge model that DENVLP vaccination substantially reduces viral replication. We also transfer the purified IgG from the immunized monkeys into immunodeficient mice, where they protect against subsequent lethal dengue virus challenge, indicating a humoral mechanism of protection. These results indicate that a DENVLP vaccine is a safe and effective vaccine candidate. One Sentence Summary: Immunization of non-human primates with a tetravalent dengue VLP vaccine induces high levels of neutralizing antibodies and reduces the severity of infection for all four dengue serotypes.

microbiology↗