Antibody responses to Zika virus proteins in pregnant and non-pregnant macaques

Abstract

24The kinetics and specificity of antibody responses against Zika virus (ZIKV) are not well-25 characterized. This is due, in part, to the antigenic similarity between ZIKV and closely 26 related Dengue virus (DENV) serotypes. Since these and other similar viruses co-27 circulate and are spread by the same mosquito species, it is difficult to disentangle 28 ZIKV-specific antibody responses from responses to closely-related arboviruses in 29 humans. Here we use high-density peptide microarrays to differentiate ZIKV from DENV 30 antibody reactivity in pregnant and non-pregnant macaque monkeys with known 31 exposure histories. We independently confirm a ZIKV-specific IgG antibody response 32 targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-33 infected people and show that antibody reactivity in pregnant animals can be detectable 34 as late as 113 days post-infection (dpi). We also show, however, these responses wane 35 over time, and in one case the response was elicited following DENV infection in a 36 previously ZIKV-exposed animal. The generally weak and short-lived antibody 37 responses to this NS2B epitope, the only reliably ZIKV-specific epitope identified to date 38 to our knowledge, suggest epidemiologic studies assessing seroprevalence specifically 39 to ZIKV using linear epitope-based strategies may be prone to false negative or 40 otherwise confounded results. These results additionally indicate some antibodies 41 produced in response to ZIKV infection are in circulation for only a short period of time. 42 43 IMPORTANCE 44Infection with ZIKV during pregnancy can lead to congenital ZIKV infection and 45 associated birth defects. The vulnerability of communities to future ZIKV outbreaks will 46 . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/352880 doi: bioRxiv preprint first posted online 3 depend, in part, on the prevalence of immunity, which is thought to be mediated 47 principally by antibodies. We currently lack diagnostic assays to differentiate ZIKV-48 specific antibodies from antibodies directed against closely related DENV and we do not 49 know how long anti-ZIKV responses persist. Here we profile antibodies recognizing 50 linear epitopes throughout the entire ZIKV and DENV polyproteins and show that while 51 ZIKV-specific antibody responses can be detected, these responses are generally weak 52 and ephemeral. This may complicate efforts to identify people previously infected with 53 ZIKV and to determine ZIKV seroprevalence, and it raises questions about the utility of 54 linear epitope-based technologies in defining ZIKV infection history. 55 56 INTRODUCTION 57

Dynamic anti-spike protein antibody profiles in COVID-19 patients

“…At present, no antiviral drug is demonstrated to be completely effective in treating COVID-19 ( Cao et al, 2020a ). Antibody-based treatment is one of the promising ways with more specificity and success in several studies, such as Zika virus ( Bailey et al, 2018 , Heffron et al, 2018 ), Hepatitis Virus C ( Brown et al, 2007 ), SARS-CoV as well as SARS-CoV-2 infection ( Butler, 2015 , Hui et al, 2018 , Mo and Fisher, 2016 , Shang et al, 2007 ). Since patient plasma contains polyclonal antibodies targeting multiple epitopes of different viral proteins, convalescent plasma therapy's success mostly relies on the broad spectrum in different individuals.…”

The landscape of antibody binding in SARS-CoV-2 infection

“…Viral protein sequences were selected and submitted to Nimble Therapeutics (Madison, WI, USA) for development into a peptide microarray [55]. Sequences represented include proteomes of all seven coronaviruses known to infect humans, proteomes of closely related coronaviruses found in bats and pangolins, and spike proteins from other coronaviruses (accession numbers and replicates per peptide shown in Supplementary Table 1).…”

“…A more stringent assessment of cross-reactivity as well as functional investigations into these cross-reactive antibodies will be vital in determining their capacity for cross-protection. Further, our methods efficiently detect antibody binding to linear epitopes 48 , but their sensitivity for detecting parts of conformational epitopes is unknown, and additional analyses will be required to determine whether epitopes identified induce neutralizing or otherwise protective antibodies. Many questions remain regarding the biology and immunology of SARS-CoV-2.…”

Rapid Response to Pandemic Threats: Immunogenic Epitope Detection of Pandemic Pathogens for Diagnostics and Vaccine Development Using Peptide Microarrays

“…Indeed, several studies using peptide microarrays focused on the identification of discriminating epitopes between certain flaviviruses. 56 − 60 For example, Viedma and colleagues 57 used a peptide microarray presenting 866 peptides of DENV serotypes 1–4, ZIKV, WNV, as well as CHIKV, a member of the family Togaviridae . By combination of experimental and computational work, they could identify peptides bound by virus specific antibodies, hence, having possible diagnostic potential.…”