Neutralizing antibody response variation against dengue 3 strains

Abstract

To evaluate the neutralizing antibody activity of a human sera panel against seven strains of the homotypic virus. Sera were collected from DENV-3 immune individuals. Two DENV-3 genotypes and strains isolated at different time-points during the 2000 and 2001-2002 Havana epidemics were included. A panel of 20 late convalescent sera collected 16-18 months after acute illness from DF and DHF patients are studied. These individuals were infected during the 2001-2002 Havana DENV-3 epidemic. All but four sera collected from DF cases had a secondary DENV-1/DENV-3 infection. Sera neutralizing antibody titer against the seven DENV-3 strains were determined by plaque reduction neutralization technique. Sera samples were tested simultaneously. Studied sera showed higher levels of neutralizing antibodies to DENV-3 strains of genotype III compared to genotype V. Interesting, higher levels of neutralizing antibodies were detected to DENV-3 strain isolated at the end of the epidemic 2001-2002. An increased tendency of GMT of neutralizing antibodies according to epidemic evolution was observed for the 2001-2002 outbreak. In general, antibody levels in sera collected from DF cases were higher. Differences in the neutralization capacity of immune DENV-3 sera tested against two homologous genotypes including strains of the same genotype are demonstrated. Observed results suggest that virus changed in the course of the epidemic. The implications of this finding in terms of dengue pathogenesis and vaccine development need to be considered.

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

“…Due to the serotype-specific nature of the neutralizing-antibody response to the E85-VRP vaccine, and based on recent observations indicating that genotypic variation within each serotype may be important in protective immunity (37,42,69,70), we examined the influence of intraserotype genotypic differences on vaccine performance. For this, we tested the ability of DENV3 E85-VRP macaque sera to neutralize DENV3 strains representing genotypes I to IV (Fig.…”

Infection Dynamics of Sylvatic Dengue Virus in a Natural Primate Host, the African Green Monkey

“…The study found, for each serotype, that (1) the vaccine (infecting) strain was robustly neutralized, (2) at least one strain was more efficiently neutralized than the vaccine strain, and (3) although all strains of DENV-1, -2, and -4 were efficiently neutralized, two of five DENV-3 strains were not. 29 The study by Blaney and others 29 and other studies 30,31 have raised concerns that there could be gaps in vaccine protection caused by strain variation. Similarly, the asymmetry in neutralization of DENV-2 NGC by monkeys infected with DENV-2 PM33971 suggests that NHP populations could be susceptible to some strains of human DENV, even if previously exposed to the homologous serotype of sylvatic DENV.…”

Antibodies Induced by Dengue Virus Type 1 and 2 Envelope Domain III Recombinant Proteins in Monkeys Neutralize Strains with Different Genotypes

“…A recent study has also demonstrated that monoclonal antibodies show differentiated neutralizing activities depending on the virulence of the strain (7). Based on the previously reported evidence (1, 4, 5, 7, 11,19,24,26), the humoral immune response induced by a vaccine candidate should be evaluated against strains of different genotypes of each serotype.Previously, we have reported that recombinant proteins containing domain III of DEN 1 or DEN 2 E proteins fused to the P64k protein from Neisseria meningitidis (PD10 and PD5, respectively) induce neutralizing antibodies and partial protection in immunized monkeys (3, 10). In the context of P64k, amino acid changes in E domain III included in the fusion protein have been involved in the antigenicity and immunogenicity of the resultant molecules in the mouse model (28).…”

“…In fact, sera from patients infected with DEN type 2 (DEN 2) or DEN 3 show variations in the neutralizing antibody responses against strains isolated early and late during the same epidemic (1,26). Preclinical studies have exposed that the primary immune responses induced after infection of mice and monkeys with DEN 2 strains belonging to both Asian and American genotypes show differences in the responses of neutralizing antibodies against the same and different strains of infection (4, 5).…”

“…A recent study has also demonstrated that monoclonal antibodies show differentiated neutralizing activities depending on the virulence of the strain (7). Based on the previously reported evidence (1,4,5,7,11,19,24,26), the humoral immune response induced by a vaccine candidate should be evaluated against strains of different genotypes of each serotype.…”