Role of Humoral versus Cellular Responses Induced by a Protective Dengue Vaccine Candidate

Raphael M. Zellweger, Robyn Miller, William E. Eddy, Laura J. White, Robert E. Johnston, Sujan Shresta.

PLoS Pathog. (2013) 9: e1003723

Speaker: Chin-Yu Chen (陳謦伃)                        Time: 13:10~14:00, Apr. 9, 2014

Commentator: Dr. Ai-Li Shiau (蕭璦莉老師)             Place: Room 601

Abstract

Dengue virus (DENV) is an arthropod-borne RNA virus of the Flaviviridae family with four serotypes. Infection with DENV can cause dengue fever, life-threatening dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). One of the mechanisms that cause DHF/DSS may be antibody-dependent enhancement (ADE). ADE, a phenomenon resulting from preexisting cross-reactive, subneutralizing antibodies (Abs), can enhance the disease severity of  a subsequent infection (1). Currently, there is no licensed vaccine available. The mechanism involved in protective dengue-vaccine candidate during DENV infection is still under evaluation. In this study, the authors wanted to assess the relative contribution of the humoral and cellular response induced by a protective dengue-vaccine candidate. They used a non-propagating vaccine vector based on Venezuelan equine encephalitis virus replicon particles (VRP) expressing the DENV2 envelope protein ectodomain (N-terminal 400 residues) as a vaccine candidate and named it E85-VRP (2). Two rounds of immunization with DENV2 E85-VRP efficiently protected AG129 mice from DENV challenge even under ADE conditions. To separate the cellular and humoral components of a protective vaccine-induced immune response, the authors transferred DENV2 E85-VRP-immunized wild-type (WT) mouse T cells, B cells, or serum into naive AG129 recipients prior to challenge with DENV. Wild-type serum or DENV2 E85-VRP-primed WT B cells had the potential to increase viral RNA levels at certain concentrations. However, T cells reduced viral burden in all conditions. These results suggest that CD8⁺ T cells contribute to protection against DENV challenge. Therefore, an efficacy dengue vaccine should focus on induce both T cell and antibody responses against dengue virus.

References

1.     Angel RMd, Valle JR-d. (2013) Dengue vaccines: strongly sought but not a reality just yet. PLoS Pathog 9: e1003551.

2.     Laura J. White, Carlos A. Sariol, Melissa D. Mattocks, Wahala M. P. B. Wahala, Vorraphun Yingsiwaphat, Martha L. Collier, Jill Whitley, Rochelle Mikkelsen, Idia V. Rodriguez, Melween I. Martinez, Aravinda de Silva, Robert E. Johnstona. (2013) An alphavirus vector based tetravalent dengue vaccine induces a rapid and protective immune response in macaques that differs qualitatively from immunity induced by live virus infection. J Virol 87: 3409–3424.