<scp>OMIP</scp>‐028: Activation panel for <scp>R</scp>hesus macaque <scp>NK</scp> cell subsets

Pomplun, Nicholas; Weisgrau, Kim L.; Evans, David T.; Rakasz, Eva G.

doi:10.1002/cyto.a.22727

Cited by 18 publications

(18 citation statements)

References 10 publications

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“…Numbers of activated and proliferating NK cells were quantified as described previously [28]. For each timepoint analyzed, 100 μL of EDTA-anticoagulated whole blood samples were incubated at room temperature for 15 minutes with an antibody master mix described in detail in Dudley et al [22].…”

Section: Methodsmentioning

confidence: 99%

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

et al. 2016

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BackgroundZika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV.Methodology/Principal FindingsUsing our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form.Conclusions/SignificanceAn effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains.

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Section: Methodsmentioning

confidence: 99%

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

et al. 2016

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“…Immunophenotyping. Numbers of activated and proliferating NK cells were quantified as described previously (Pomplun et al, 2015). For each timepoint analyzed, 100 μL of EDTA-anticoagulated whole blood samples were incubated at room temperature for 15 minutes with an antibody master mix described in detail in (Dudley et al, 2016).…”

Section: Comparison Of East African Zikv Mr766 and Asian Zika Virus Imentioning

confidence: 99%

Heterologous protection against Asian Zika virus challenge in rhesus macaques

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Dudley

Newman

et al. 2016

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words; 150 word max)Zika virus (ZIKV) isolates are genetically diverse, but belong to two recognized lineages, termed "African" and "Asian." Asian ZIKV infection during pregnancy causes fetal abnormalities including microcephaly. Developing an effective preventative Zika virus vaccine that protects pregnant women is essential for minimizing fetal abnormalities; at least 18 groups are developing ZIKV vaccines (Hayden, 2016). The genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, and the degree to which immunity against one ZIKV strain could provide protection against another is unknown. Here we show that rhesus macaques infected with East African ZIKV strain MR766 are completely protected from subsequent infection with heterologous Asian ZIKV. MR766 is more genetically divergent from all known Asian ZIKV strains than Asian ZIKV strains are from one another. Therefore, ZIKV strain selection is unlikely to compromise vaccine effectiveness. Highlights (85 characters max per bullet point)• African Zika virus (ZIKV) strain MR766 productively infects macaques (68 characters)• Immunity elicited by MR766 protects macaques against heterologous Asian ZIKV (77 characters)• In vivo restoration of a putative N-linked glycosylation site in MR766 (70 characters)• Immunogen selection is unlikely to adversely affect the breadth of vaccine protection (85 characters) eTOC (52 words; 80 words max) An effective Zika virus vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses are primed by infection with East African ZIKV are completely protected from reinfection with heterologous Asian ZIKV. Any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains.

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“…As we previously reported in OMIP‐028 , the availability of antibodies recognizing certain rhesus‐antigens is rather limited. For example, there is only one antibody (clone Z199) specific to NKG2A (CD159a) in humans that cross‐reacts with rhesus samples.…”

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confidence: 98%

OMIP‐035: Functional analysis of natural killer cell subsets in macaques

et al. 2016

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This panel was developed to measure the functional capability of natural killer (NK) cell subsets in rhesus macaques (Macaca mulatta). It includes markers to determine the frequency of cytokine secreting and cytotoxic NK cell subpopulations in peripheral blood mononuclear cell (PBMC) samples stimulated in vitro with human 721.221 cells. NK cell subsets were defined by the expression of killer cell immunoglobulin-like receptors (KIRs) Mamu-KIR3DL01 and Mamu-KIR3DL05, and differentiation antigens CD16 and CD56. The panel can be used to assess the functional capability of NK cells in a range of normal and pathologic conditions of captive bred rhesus macaques of Indian origin. V

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OMIP‐028: Activation panel for Rhesus macaque NK cell subsets

Cited by 18 publications

References 10 publications

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

Heterologous protection against Asian Zika virus challenge in rhesus macaques

OMIP‐035: Functional analysis of natural killer cell subsets in macaques

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