Safety and immunogenicity of a recombinant tetravalent dengue vaccine in 9-16 year olds: a randomized, controlled, phase II trial in Latin America.
BACKGROUND
The dengue virus is a member of the Flavivirus (FV) genus, which also includes the yellow fever virus. Dengue disease is caused by any 1 of 4 dengue virus serotypes and is a serious public health concern in Latin America. This study evaluated the safety and immunogenicity of a candidate recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in 9-16 year olds in Latin America.


METHODS
In this randomized, blinded, controlled study, volunteers received either 3 doses of CYD-TDV (n = 401) or placebo as first and second injection and tetanus/diphtheria/acellular pertussis vaccine as third injection (n = 199) at 0, 6 and 12 months. Adverse events were documented. Plaque reduction neutralization test antibody titers against the 4 CYD-TDV parental strains were measured before and 28 days after each dose. Seropositivity was defined as antibody titers ≥10 1/dil.


RESULTS
The number of adverse reactions decreased after each successive CYD-TDV dose. After each CYD-TDV dose, antibody titers against all 4 serotypes were higher than baseline and respective predose titers. After the third dose of CYD-TDV, 100%, 98.6% and 93.4% of participants were seropositive for at least 2, at least 3 or all 4 serotypes, respectively. Higher antibody titers were observed in participants in the CYD-TDV group who were FV-seropositive at baseline compared with those who were FV-seronegative.


CONCLUSIONS
CYD-TDV had a favorable safety profile and elicited antibody responses against all 4 dengue virus serotypes in 9-16 year olds in Latin America. These findings support the continued development of CYD-TDV.
From the *Centro de Investigaciones Epidemiológicas, Universidad Industrial de Santander, Bucaramanga, Colombia; †Organización para el Desarrollo y la Investigación Salud en Honduras, Tegucigalpa, Honduras; ‡Instituto Nacional de Pediatría, Unidad de Apoyo a la Investigación Clínica, Mexico City, Mexico; §Sanofi Pasteur, Swiftwater, PA; ¶Sanofi Pasteur, Montevideo, Uruguay; ‖Sanofi Pasteur, Bogota, Colombia; and **Sanofi Pasteur, Mexico City, Mexico.
Luis Á
LÁ
Villar
Doris M
DM
Rivera-Medina
José Luis
JL
Arredondo-García
Mark
M
Boaz
Linda
L
Starr-Spires
Manoj
M
Thakur
Betzana
B
Zambrano
María C
MC
Miranda
Enrique
E
Rivas
Gustavo H
GH
Dayan
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D006801:Humans; D007843:Latin America; D008297:Male; D016037:Single-Blind Method; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014614:Vaccines, Synthetic