Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children

Abstract

Dengue fever, caused by four serotypes of a mosquito-borne virus, is a growing problem in tropical countries. Currently, there is no treatment or vaccine. We evaluated safety and immunogenicity of two doses, given six months apart, of seven formulations of dengue tetravalent live-attenuated vaccine (containing different concentrations of the component viruses) versus placebo in 59 flavivirus-seronegative Thai adults. The first dose was the more reac-togenic. Most volunteers experienced clinically moderate fever, headache, myalgia, eye pain or rash 7-11 days after injection, generally lasting three days or less. Modest decreases in platelets and neutrophils were observed. After one dose, 58% of dengue recipients seroconverted (neutralizing antibody level 1:10) against 3 serotypes; 35% sero-converted against all four. After the second dose, seroconversion was 76% and 71%, respectively. All subjects sero-converted to serotype 3 after one dose. Serotype 4 elicited the lowest primary response but the highest increase in seroconversion after the second dose.

Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys

“…A major problem with previously evaluated TVs has been their capacity to cause a DEN-like illness in vaccinees (11,26,38). This reactogenicity appears to be related to a high level of replication of at least one of the components of the TV.…”

Forecasting dengue vaccine demand in disease endemic and non-endemic countries

“…Initial immunogenicity data of live-attenuated dengue vaccines among persons with no previous DENV exposure shows that 3 doses are required over a 12 month period. 23 Such a schedule would limit use of this vaccine to highly selected populations of overseas workers, frequent travelers, or the military. Studies have shown that the majority of travelers seek pre-travel health advice less than 1 month before departure which makes a vaccine with 6 or even 12 months dose spacing difficult in this population.…”

Dengue: defining protective versus pathologic immunity

“…DNA vaccines consisting of plasmids expressing one or a few proteins from each DENV serotype are in an earlier stage of development, as are subunit vaccines based on purified recombinant DENV proteins (23,24). Several of these approaches have demonstrated protective efficacy in animal models of DENV infection, and a few have shown safety and immunogenicity in early phase clinical studies (14,18,25,26).…”