Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques

Neil Berry,Neil Almond,Claire Ham,Elaine Giles,Jo Hall,Debbie Ferguson,Sarah Kempster,Giada Mattiuzzo,Roger Hewson,Mark Page,Yemisi Adedeji,Adrian Jenkins

doi:10.1038/s41541-020-00234-y

Neil Berry, Neil Almond + Show 10 more

Open Access

https://doi.org/10.1038/s41541-020-00234-y

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Abstract

Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

Highlights

Zika virus (ZIKV) is a Flavivirus and newly re-emergent human pathogen prevalent in parts of Central and South America[1], having spread from Africa and Asia across the Pacific Ocean in the previous decade[2]
Relating outcomes of model systems back to standardised measures of vaccine protection will be important in assessing correlates of vaccine protection elicited by different vaccines
To address this we have utilised human convalescent plasma derived from two ZIKV-exposed individuals during the recent epidemic in central America, who subsequently recovered from infection making a strong humoral immune response

Summary

INTRODUCTION

Zika virus (ZIKV) is a Flavivirus and newly re-emergent human pathogen prevalent in parts of Central and South America[1], having spread from Africa and Asia across the Pacific Ocean in the previous decade[2]. There was no evidence of late appearance or delayed viral kinetics (vRNA blips) at subsequent time-points, indicating complete virus suppression at the anticipated time of the acute-phase viraemia This is further supported by lack of detectable ZIKV genome in any tissue analysed by cell associatedRNA RT-qPCR representing key tissues of the spleen, the iliac, and brachial (peripheral) lymph nodes, or mesenteric, salivary gland and genital lymph nodes. 3 and 4, measuring IgG and IgM responses to whole virus antigens and the NS-1 protein, as well as neutralising antibody levels In this manner serological responses were compared pre- and post-administration of ZIKVPRVABC59 for the four naïve controls and four macaques receiving passively transferred human plasma. Post-ZIKV challenge there was some fluctuation noted in macaque R1 which exhibited a small boost in both neutralising antibody, anti-NS-1, and total IgG levels, detected 3 days post administration of virus (Fig. 3a–c). None of the serological responses detected are compatible with an active anti-ZIKV response in any of the immunised macaques

DISCUSSION

Study design

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