Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice

Branche, Emilie; Simon, Ayo Yila; Sheets, Nicholas; Kim, Kenneth S.; Barker, Douglas C.; Nguyen, Anh-Viet; Sahota, Harpreet; Young, Matthew P.; Salgado, Rebecca; Mamidi, Anila; Viramontes, Karla M.; Carnelley, Trevor; Qiu, Hongyu; Ngono, Annie Elong; Regla-Nava, José Ángel; Susantono, Mercylia; Cuevas, Joan M. Valls; Kennedy, Kieron; Kodihalli, Shantha; Shresta, Sujan

doi:10.1038/s41598-019-46291-9

Cited by 12 publications

(18 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[27][28][29][30][31] Hence, the role of T cells has been thoroughly investigated in dengue, [32][33][34][35][36][37][38][39][40][41] yellow fever, [42][43][44] Zika, 45 and other flavivirus diseases. 46 Although an important role of antibodies has been established in ZIKV experimental models, 47,48 the role of T cells has also been appreciated. 11,47,49,50 In particular, CD8+ T cells have been found to be an important determinant of resistance in the absence of type I IFN 10,49 and to display a phenotype associated with cytotoxicity and production of IFN , TNF, or both.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional T cell response in convalescent patients two years after ZIKV infection

Neto

Gonçalves-Pereira

Queiroz

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Zika is an important emerging infectious disease in which the role of T cells remains elusive. This study aimed to evaluate the phenotype of multifunctional T cells in individuals 2 yr after exposure to Zika virus (ZIKV). We used a library of 671 synthetic peptides covering the whole polyprotein of ZIKV in pools corresponding to each viral protein (i.e., capsid, membrane precursor or prM, envelope, NS1 [nonstructural protein], NS2A + NS2B, NS3, NS4A + NS4B, and NS5) to stimulate PBMCs from individuals previously exposed to ZIKV. We observed an increased frequency of ZIKV-specific IFN , IL-17A, TNF, and IL-10 production by T cell populations. IFN and TNF production were especially stimulated by prM, capsid, or NS1 in CD8+ T cells and by capsid or prM in CD4+ T cells. In addition, there was an increase in the frequency of IL-10+ CD8+ T cells after stimulation with prM, capsid, NS1, NS3, or NS5. Multifunctional properties were observed in ZIKVspecific T cells responding especially to prM, capsid, NS1 or, to a smaller extent, NS3 antigens. For example, we found a consistent IFN + TNF+ CD8+ T cell population in response to most virus antigens and CD4+ and CD8+ T cells that were IFN + IL-17A+ and IL-17A+IL-10+, which could also produce TNF, in response to capsid, prM, NS1, or NS3 stimulation. Interestingly, CD8+ T cells were more prone to a multifunctional phenotype than CD4+ T cells, and multifunctional T cells were more efficient at producing cytokines than single-function cells. This work provides relevant insights into the quality of ZIKV-specific T cell responses and ZIKV immunity. K E Y W O R D S immunity, multifunctional T cells, Zika, ZIKV 1 INTRODUCTION Zika virus (ZIKV) is an arbovirus of the Flaviviridae family and Flavivirus genus that comprises more than 70 viruses distributed worldwide, among which approximately 40 viruses are described as causing diseases in humans. 1 Among the Flavivirus viruses of particular interest, Abbreviations: CZS, Congenital Zika syndrome; DENV, Dengue virus; MFI, mean fluorescence intensity; NS, nonstructural protein; prM, membrane precursor; Tc, CD8+ cytotoxic T cell; YFV, Yellow fever virus; ZIKV, Zika virus. the most prominent members are dengue virus (DENV), responsible for an annual incidence of 96 million infections with symptomatic dengue fever; yellow fever virus (YFV); West Nile virus (WNV); Japanese encephalitis virus (JEV); and ZIKV, which are classified as emerging infectious viruses. 1 It is estimated that only 20-25% of ZIKV-infected individuals develop symptoms, with nonspecific clinical manifestations common to other arboviruses, 2 such as rash, low-grade fever, nonpurulent conjunctivitis, myalgia, and arthritis/arthralgia, which are usually benign and self-limiting. ZIKV infection has also been associated with

show abstract

Section: Discussionmentioning

confidence: 99%

Multifunctional T cell response in convalescent patients two years after ZIKV infection

Neto

Gonçalves-Pereira

Queiroz

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…CP was tested and showed efficacy (Table 2); however, HIG offered several advantages as a sustainable therapeutic option to provide a bridge between the outbreak and vaccine availability and to be administered upon infection to deliver immediate protection. Therefore, development of HIGs was evaluated 100,[130][131][132] for prophylaxis of ZIKV infection in at-risk populations, including women of childbearing potential and pregnant women. ZIKV-HIG, manufactured from human plasma with high titers of anti-ZIKV antibodies, was shown to prevent and/or neutralize ZIKV infection in preclinical studies using an immune-deficient mouse model (Ifnar1 -/-).…”

Section: Zika Virusmentioning

confidence: 99%

Polyclonal hyper immunoglobulin: A proven treatment and prophylaxis platform for passive immunization to address existing and emerging diseases

Tharmalingam

Han

Wozniak

et al. 2021

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Passive immunization with polyclonal hyper immunoglobulin (HIG) therapy represents a proven strategy by transferring immunoglobulins to patients to confer immediate protection against a range of pathogens including infectious agents and toxins. Distinct from active immunization, the protection is passive and the immunoglobulins will clear from the system; therefore, administration of an effective dose must be maintained for prophylaxis or treatment until a natural adaptive immune response is mounted or the pathogen/agent is cleared. The current review provides an overview of this technology, key considerations to address different pathogens, and suggested improvements. The review will reflect on key learnings from development of HIGs in the response to public health threats due to Zika, influenza, and severe acute respiratory syndrome coronavirus 2.

show abstract

“…As has been demonstrated previously for multiple flavivirus infections [ 23 , 24 , 25 ], ZIKV-specific polyclonal and monoclonal neutralizing antibody responses can protect mice and nonhuman primates from mortality and severe disease. There is also a role for non-neutralizing antibodies to protect against ZIKV disease [ 22 , 26 , 27 , 28 ]. These data highlight the necessity for a ZIKV vaccine that induces robust T cell and B cell responses for protection against disease.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and Efficacy of a Recombinant Human Adenovirus Type 5 Vaccine against Zika Virus

et al. 2020

View full text Add to dashboard Cite

Zika virus (ZIKV) is a significant public health concern due to the pathogen's ability to be transmitted by either mosquito bite or sexual transmission, allowing spread to occur throughout the world. The potential consequences of ZIKV infection to human health, specifically neonates, necessitates the development of a safe and effective Zika virus vaccine. Here, we developed an intranasal Zika vaccine based upon the replication-deficient human adenovirus serotype 5 (hAd5) expressing ZIKV pre-membrane and envelope protein (hAd5-ZKV). The hAd5-ZKV vaccine is able to induce both cell-mediated and humoral immune responses to ZIKV epitopes. Importantly, this vaccine generated CD8 + T cells specific for a dominant ZIKV T cell epitope and is shown to be protective against a ZIKV challenge by using a pre-clinical model of ZIKV disease. We also demonstrate that the vaccine expresses pre-membrane and envelope protein in a confirmation recognized by ZIKV experienced individuals. Our studies demonstrate that this adenovirus-based vaccine expressing ZIKV proteins is immunogenic and protective in mice, and it encodes ZIKV proteins in a conformation recognized by the human antibody repertoire.The development of a ZIKV vaccine is urgent due to the speed of ZIKV spread in susceptible populations, as well as the range of diseases caused by infection [5]. According to the World Health Organization (WHO), a majority of individuals who are infected with ZIKV are asymptomatic, but those with a mild clinical form of the disease report symptoms including fever, rash, conjunctivitis, and muscle and joint pain, all of which typically last less than a week. While these symptoms are rarely debilitating, complications of Zika virus disease can include Guillain-Barré syndrome. Zika-induced microcephaly and congenital abnormalities are generally classified as congenital Zika syndrome (CZS), which is also a potential complication in the developing fetuses of pregnant women [4,6-10]. These risks, combined with the explosive outbreaks that occurred at Yap Island in 2007 [11], French Polynesia in 2013 [12], and Brazil in 2015-16 [13], underscore the need to control the spread of ZIKV. However, there are no current FDA-approved vaccines available to control infection.Harnessing the power of both arms of the adaptive immune response improves vaccine potency and efficacy while reducing opportunities of viral escape. Current data from both naturally acquired human infection and mouse models of ZIKV disease indicate that protection from disease is multi-faceted (reviewed in [14][15][16][17][18]). Both small and large animal models of ZIKV infection have demonstrated that the Zika-specific CD8 + and CD4 + T cell response is necessary and sufficient to protect against a lethal ZIKV challenge [19][20][21][22]. As has been demonstrated previously for multiple flavivirus infections [23-25], ZIKV-specific polyclonal and monoclonal neutralizing antibody responses can protect mice and nonhuman primates from mortality and severe disease. There is also a role fo...

show abstract

Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice

Cited by 12 publications

References 89 publications

Multifunctional T cell response in convalescent patients two years after ZIKV infection

Multifunctional T cell response in convalescent patients two years after ZIKV infection

Polyclonal hyper immunoglobulin: A proven treatment and prophylaxis platform for passive immunization to address existing and emerging diseases

Immunogenicity and Efficacy of a Recombinant Human Adenovirus Type 5 Vaccine against Zika Virus

Contact Info

Product

Resources

About