Humoral and cellular immune dynamics following Zika virus secondary challenge in non-human primates.
J. M. Richner, S. R. Cleary, N. Podkanski, M. Mali, R. Baker
Zika virus recently emerged into the Western hemisphere leading to more than 580,000 suspected cases in South, Central, and North America from 2015 to the present. The current outbreak has been linked to neurological disorders such as Guillain-Barré syndrome and defects in the developing fetus characterized by placental insufficiency, microcephaly, ocular abnormalities, and increased risk of miscarriages. Mouse models of Zika virus disease, while useful, have limitations in the study of immune responses as these animals are refractory to a natural Zika virus infection. On the other hand, non-human primates are the natural reservoir of Zika virus and represent the model that most accurately reflects human pathogenesis and immunity. Assessment of the immune response dynamics following a Zika virus infection will influence our understanding of natural immunity. Furthermore, characterizing the immune response to a secondary Zika virus challenge will help to define the parameters of a protective immune response and gauge vaccine efficacy. In this study, we challenged 6 rhesus macaques that had previously been infected with Zika virus. Serum and PBMCs were collected at pre-challenge and days 7, 14, 29, 49, 63, 77, 91, and 105 post challenge. Humoral immune responses were analyzed by serum neutralization assays and were found to peak at day 14 after secondary challenge. Antiviral T cell responses against the viral envelope protein were evaluated by intracellular cytokine staining and flow cytometry. Antiviral T cell dynamics also spiked at day 14 after secondary challenge, but levels remained elevated past day 29 post infection. A majority of the antiviral CD8+ and CD4+ T cells were polyfunctional (CD8+ expressing IFNg and TNFa, and CD4+ T cells expressing TNFa and IL2). This study highlights the memory recall response against a secondary Zika challenge. Further studies will determine how these findings compare to novel vaccination strategies which elicit immunologic memory.