Electroporation-Mediated Immunization of a Candidate DNA Vaccine Expressing Dengue Virus Serotype 4 prM-E Antigen Confers Long-Term Protection in Mice

Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.

Seroepidemiologic study on convalescent sera from dengue fever patients in Jinghong,Yunnan

After dengue virus(DENV)infection,antibody-dependent enhancement(ADE)is easy to occur when the neutralizing antibody(NAb)gradually decreases to a sub-neutralizing concentration.In this cohort surveillance,we utilized sera samples collected from dengue fever patients at different convalescent phases in Jinghong City,to investigate the dynamic change rule of DENV-specific antibodies,and to analyze the risk of ADE caused by secondary infection with heterologous serotypes DENVs.For baseline serosurvey,191 four-year and 99 six-year sera samples during convalescence were collected in 2017 and 2019,respectively.The positive rate of DENVspecific immunoglobulin G was 98.4%in 2017,which significantly decreased to 82.8%in 2019.The geometric mean titer(GMT)of NAb decreased from 1:155.35 to 1:46.66.Among 290 overall samples,73 paired consecutive samples were used for follow-up serosurvey.In four-year sera,the GMTs of NAb against DENV-3 and cross-reactive antibodies against DENV-1,DENV-2 and DENV-4 were 1:167.70,1:13.80,1:18.54 and 1:45.26,respectively,which decreased to 1:53.18,1:10.30,1:14.60 and 1:8.17 in six-year sera.In age-stratified analysis,due to the increasing number of ADE positive samples from 2017 to 2019 in 31–40 and 51–60 years groups,the risk of ADE in DENV-4 infection was positively associated with the extension of convalescent phase,and the odd ratio was higher than other groups.With the recovery period lengthened,the risk of secondary infection with DENV-1 and DENV-2 was reduced.Our results offer essential experimental data for risk prediction of severe dengue in hyper-endemic dengue areas,and provide crucial scientific insight for the development of effective dengue vaccines.