DiazGranados Carlos A, Langevin Edith, Bonaparte Matthew, Sridhar Saranya, Machabert Tifany, Dayan Gustavo, Forrat Rémi, Savarino Stephen
Sanofi Pasteur, Marcy l'Etoile, France.
Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
Clin Infect Dis. 2021 May 18;72(10):1730-1737. doi: 10.1093/cid/ciaa304.
The immune profile of dengue-experienced individuals is a determinant of dengue reinfection severity risk. Individuals with a single prior dengue infection (monotypic) are at highest risk for severe disease, while individuals with ≥ 2 prior dengue infections (multitypic) are at lower risk. The tetravalent dengue vaccine (CYD-TDV) has shown efficacy in the prevention of dengue in individuals with prior dengue infection. We estimated efficacy in individuals with monotypic or multitypic immune profiles.
Participants enrolled in the immunogenicity subsets of 2 randomized placebo-controlled phase 3 studies (CYD14, NCT01373281; CYD15, NCT01374516) were classified as either monotypic or multitypic, based on measured baseline dengue plaque reduction neutralization test. Vaccine efficacy (VE) against symptomatic virologically confirmed dengue (VCD) was assessed over 25 months and against VCD hospitalization over 6 years.
Of 3927 participants in the immunogenicity subsets, 496 and 257 in the CYD-TDV and placebo groups, respectively, were classified as monotypic immune, and 1227 and 612, respectively, as multitypic immune. VE against symptomatic VCD was 77.4% (95% CI, 56.4%-88.2%) for monotypic and 89.2% (95% CI, 71.5%-95.9%) for multitypic profiles, with corresponding absolute risk reductions (ARRs) of 4.48% (95% CI, 2.32%-6.65%) for monotypics and 1.67% (95% CI, .89%-2.46%) for multitypics. VE against hospitalized VCD was 75.3% (95% CI, 42.7%-90.2%) in monotypics and 81.2% (95% CI, 21.7%-96.8%) in multitypics, with ARRs of 0.95% (95% CI, .37%-1.53%) for monotypics and 0.18% (95% CI, .02%-.34%) for multitypics.
CYD-TDV benefits individuals with monotypic and multitypic immune profiles. Larger public health benefit is expected to derive from the protection of individuals with a monotypic immune profile.
既往感染过登革热的个体的免疫状况是登革热再感染严重程度风险的决定因素。既往仅有一次登革热感染（单型）的个体患重症疾病的风险最高，而既往有≥2次登革热感染（多型）的个体风险较低。四价登革热疫苗（CYD-TDV）已显示出对既往感染过登革热的个体预防登革热的效果。我们评估了其对单型或多型免疫状况个体的效果。
根据测量的基线登革热蚀斑减少中和试验，将参与2项随机安慰剂对照3期研究（CYD14，NCT01373281；CYD15，NCT01374516）免疫原性子集的参与者分为单型或多型。在25个月内评估疫苗对有症状的病毒学确诊登革热（VCD）的效力（VE），并在6年内评估对VCD住院治疗的效力。
在免疫原性子集的3927名参与者中，CYD-TDV组和安慰剂组分别有496名和257名被分类为单型免疫，分别有1227名和612名被分类为多型免疫。对有症状的VCD的VE，单型为77.4%（95%CI，56.4%-88.2%），多型为89.2%（95%CI，71.5%-95.9%），单型相应的绝对风险降低（ARR）为4.48%（95%CI，2.32%-6.65%），多型为1.67%（95%CI，0.89%-2.46%）。对住院VCD的VE，单型为75.3%（95%CI，42.7%-90.2%），多型为81.2%（95%CI，21.7%-96.8%），单型的ARR为0.95%（95%CI，0.37%-1.53%），多型为0.18%（95%CI，0.02%-0.34%）。
CYD-TDV对单型和多型免疫状况的个体均有益。预计对单型免疫状况个体的保护将带来更大的公共卫生效益。
