Antibody to Dengue 1 Detected More Than 60 Years after Infection

Abstract

We investigated the duration of humoral responses to dengue virus infection in individuals who recalled experiencing dengue fever-like illnesses at the time of the Second World War, when dengue fever epidemics occurred throughout the Pacific and Southeast Asia. In July 1943 dengue fever reappeared in Hawaii following an interval of 31 years. Over the next 12 months a total of 1498 locally transmitted cases were reported, and at least 46 imported cases were identified, most of which were among members of the military returning from the Pacific Theatre of the war. Serum samples collected in 2005, more than 60 years after onset of symptoms, were tested for the presence of dengue-specific antibodies using a rapid ELISA test, and by plaque reduction neutralization test. Four of seven samples were positive for dengue-specific IgG and demonstrated neutralization titers ≥160 to dengue 1. We describe the existence of dengue-specific antibodies in the serum of people infected more than 60 years earlier. BRIEF REPORTDengue Viruses Are mosquito-borne single-stranded RNA viruses that belong to the family Flaviviridae. Infection with any of the four dengue serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) can cause a spectrum of illnesses ranging from asymptomatic infection to severe hemorrhagic disease and shock syndrome, which can be fatal. Immunity to one dengue serotype following a first, or primary, infection does not protect against subsequent infection with any of the other three serotypes, and indeed, epidemiological observations suggest that severe disease occurs more frequently in the setting of secondary infection with heterologous virus (reviewed in 6 , 7). The pathogenesis of the severe forms of disease is not fully understood, but one hypothesis is based on the idea of antibody-dependent enhancement, in which preexisting non-neutralizing antibodies induced during the first dengue infection enhance infection of mononuclear cells during the second infection via cell surface FcγR (9, reviewed in 13). Thus, persistence of dengue-specific antibody may be a significant risk factor for development of severe disease in countries where dengue is hyperendemic.

Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection

“…In contrast, inhibition of theh uptake of heterologous serotypes by the early convalescent sera from patients with primary DENV infection was observed only at low serum dilutions. This process may be the reason why a person can be transiently immune to the remaining three serotypes of DENV following an acute primary DENV infection (41,42). Further studies, however, would be needed to establish this notion.…”

Inhibition of dengue virus replication by diisopropyl chrysin-7-yl phosphate

“…We found that CPI was highly effective against both DENV1 and DENV2 replication in cell cultures without obvious cytotoxicity. Together with other viruses, DENV infection usually induces generation of neutralizing antibodies, which protect the individuals from viral infection and even provide life-long protection against the homologous serotype (Imrie et al, 2007). Unfortunately, in a secondary infection by a different DENV serotype, the antibody from the previous infection could cross-react with the virus to form a non-neutralizing complex and result in enhancement of viral infection through a mechanism known as antibody-depen-dent enhancement (Halstead, 2003).…”

Mapping the Human Memory B Cell and Serum Neutralizing Antibody Responses to Dengue Virus Serotype 4 Infection and Vaccination

“…A primary DENV infection provides lifelong protection against disease caused by the infecting homologous serotype in most subjects (6). A secondary infection with virus of a heterologous serotype increases the risk of developing severe dengue hemorrhagic fever (7).…”