Bio

Professional Education


  • Doctor of Philosophy, Johns Hopkins University (2009)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


Antigen-specific B and T cells, mucosal immunology, humoral memory, antibodies, virology, vaccinology, public health.

Publications

Journal Articles


  • Combinatorial tetramer staining and mass cytometry analysis facilitate T-cell epitope mapping and characterization NATURE BIOTECHNOLOGY Newell, E. W., Sigal, N., Nair, N., Kidd, B. A., Greenberg, H. B., Davis, M. M. 2013; 31 (7): 623-U81

    Abstract

    It is currently not possible to predict which epitopes will be recognized by T cells in different individuals. This is a barrier to the thorough analysis and understanding of T-cell responses after vaccination or infection. Here, by combining mass cytometry with combinatorial peptide-MHC tetramer staining, we have developed a method allowing the rapid and simultaneous identification and characterization of T cells specific for many epitopes. We use this to screen up to 109 different peptide-MHC tetramers in a single human blood sample, while still retaining at least 23 labels to analyze other markers of T-cell phenotype and function. Among 77 candidate rotavirus epitopes, we identified six T-cell epitopes restricted to human leukocyte antigen (HLA)-A*0201 in the blood of healthy individuals. T cells specific for epitopes in the rotavirus VP3 protein displayed a distinct phenotype and were present at high frequencies in intestinal epithelium. This approach should be useful for the comprehensive analysis of T-cell responses to infectious diseases or vaccines.

    View details for DOI 10.1038/nbt.2593

    View details for Web of Science ID 000321579700019

    View details for PubMedID 23748502

  • Optimized fluorescent labeling to identify memory B cells specific for Neisseria meningitidis serogroup B vaccine antigens ex vivo IMMUNITY, INFLAMMATION AND DISEASE Nair, N., Buti, L., Faenzi, E., Buricchi, F., Nuti, S., Sammichelli, C., Tavarini, S., Popp, M. W., Ploegh, H., Berti, F., Pizza, M., Castellino, F., Finco, O., Rappuoli, R., Del Giudice, G., Galli, G., Bardelli, M. 2013; 1 (1)

    View details for DOI 10.1002/iid3.3

  • Innate immune response to homologous rotavirus infection in the small intestinal villous epithelium at single-cell resolution PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sen, A., Rothenberg, M. E., Mukherjee, G., Feng, N., Kalisky, T., Nair, N., Johnstone, I. M., Clarke, M. F., Greenberg, H. B. 2012; 109 (50): 20667-20672

    Abstract

    "Bulk" measurements of antiviral innate immune responses from pooled cells yield averaged signals and do not reveal underlying signaling heterogeneity in infected and bystander single cells. We examined such heterogeneity in the small intestine during rotavirus (RV) infection. Murine RV EW robustly activated type I IFNs and several antiviral genes (IFN-stimulated genes) in the intestine by bulk analysis, the source of induced IFNs primarily being hematopoietic cells. Flow cytometry and microfluidics-based single-cell multiplex RT-PCR allowed dissection of IFN responses in single RV-infected and bystander intestinal epithelial cells (IECs). EW replicates in IEC subsets differing in their basal type I IFN transcription and induces IRF3-dependent and IRF3-augmented transcription, but not NF-?B-dependent or type I IFN transcripts. Bystander cells did not display enhanced type I IFN transcription but had elevated levels of certain IFN-stimulated genes, presumably in response to exogenous IFNs secreted from immune cells. Comparison of IRF3 and NF-?B induction in STAT1(-/-) mice revealed that murine but not simian RRV mediated accumulation of IkB-? protein and decreased transcription of NF-?B-dependent genes. RRV replication was significantly rescued in IFN types I and II, as well as STAT1 (IFN types I, II, and III) deficient mice in contrast to EW, which was only modestly sensitive to IFNs I and II. Resolution of "averaged" innate immune responses in single IECs thus revealed unexpected heterogeneity in both the induction and subversion of early host antiviral immunity, which modulated host range.

    View details for DOI 10.1073/pnas.1212188109

    View details for Web of Science ID 000312605600104

    View details for PubMedID 23188796

  • HIV-1 Infection in Zambian Children Impairs the Development and Avidity Maturation of Measles Virus-Specific Immunoglobulin G after Vaccination and Infection JOURNAL OF INFECTIOUS DISEASES Nair, N., Moss, W. J., Scott, S., Mugala, N., Ndhlovu, Z. M., Lilo, K., Ryon, J. J., Monze, M., Quinn, T. C., Cousens, S., Cutts, F., Griffin, D. E. 2009; 200 (7): 1031-1038

    Abstract

    Endemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects that HIV infection has on immune responses to measles and to measles vaccine can impact measles elimination efforts. Assays to measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) to all measles virus (MV) proteins, and the plaque reduction neutralization (PRN) assay, which measures antibody to the hemagglutinin and correlates with protection. Antibody avidity may affect neutralizing capacity.HIV-infected and HIV-uninfected Zambian children were studied after measles vaccination (n=44) or MV infection (n=57). Laboratory or wild-type MV strains were used to infect Vero or Vero/signaling lymphocyte-activation molecule (SLAM) cells in PRN assays. IgG to MV was measured by EIA, and avidity was determined by ammonium thiocyanate dissociation.HIV infection impaired EIA IgG responses after vaccination and measles but not PRN responses measured using laboratory-adapted MV. Avidity was lower among HIV-infected children 3 months after vaccination and 1 and 3 months after measles. Neutralization of wild-type MV infection of Vero/SLAM cells correlated with IgG avidity.Lower antibody quality and quantity in HIV-infected children after measles vaccination raise challenges for assuring the long-term protection of these children. Antibody quality in children receiving antiretroviral therapy requires assessment.

    View details for DOI 10.1086/605648

    View details for Web of Science ID 000269475000004

    View details for PubMedID 19702505

  • Use of vaxfectin adjuvant with DNA vaccine encoding the measles virus hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques against measles virus CLINICAL AND VACCINE IMMUNOLOGY Pan, C., Jimenez, G. S., Nair, N., Wei, Q., Adams, R. J., Polack, F. P., Rolland, A., Vilalta, A., Griffin, D. E. 2008; 15 (8): 1214-1221

    Abstract

    A measles virus vaccine for infants under 6 months of age would help control measles. DNA vaccines hold promise, but none has provided full protection from challenge. Codon-optimized plasmid DNAs encoding the measles virus hemagglutinin and fusion glycoproteins were formulated with the cationic lipid-based adjuvant Vaxfectin. In mice, antibody and gamma interferon (IFN-gamma) production were increased by two- to threefold. In macaques, juveniles vaccinated at 0 and 28 days with 500 microg of DNA intradermally or with 1 mg intramuscularly developed sustained neutralizing antibody and H- and F-specific IFN-gamma responses. Infant monkeys developed sustained neutralizing antibody and T cells secreting IFN-gamma and interleukin-4. Twelve to 15 months after vaccination, vaccinated monkeys were protected from an intratracheal challenge: viremia was undetectable by cocultivation and rashes did not appear, while two naïve monkeys developed viremia and rashes. The use of Vaxfectin-formulated DNA is a promising approach to the development of a measles vaccine for young infants.

    View details for DOI 10.1128/CVI.00120-08

    View details for Web of Science ID 000258667200011

    View details for PubMedID 18524884

  • Dose-dependent protection against or exacerbation of disease by a polylactide glycolide microparticle-adsorbed, alphavirus-based measles virus DNA vaccine in rhesus macaques CLINICAL AND VACCINE IMMUNOLOGY Pan, C., Nair, N., Adams, R. J., Zink, M. C., Lee, E., Polack, F. P., Singh, M., O'Hagan, D. T., Griffin, D. E. 2008; 15 (4): 697-706

    Abstract

    Measles remains an important cause of vaccine-preventable child mortality. Development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. DNA vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. In the current study, we evaluated the use of a layered alphavirus DNA/RNA vector encoding measles virus H (SINCP-H) adsorbed onto polylactide glycolide (PLG) microparticles. In mice, antibody and T-cell responses to PLG-formulated DNA were substantially improved compared to those to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5 mg) or intradermally (0.5 or 0.1 mg). Antibody and T-cell responses were induced but not sustained. On challenge, the intramuscularly vaccinated monkeys did not develop rashes and had lower viremias than vector-treated control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. Monkeys vaccinated intradermally with the low dose developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia, and higher viremia compared to vector-treated control monkeys. Protection after challenge correlated with gamma interferon-producing T cells and with early production of high-avidity antibody that bound wild-type H protein. We conclude that PLG/SINCP-H is most efficacious when delivered intramuscularly but does not provide an advantage over standard DNA vaccines for protection against measles.

    View details for DOI 10.1128/CVI.00045-08

    View details for Web of Science ID 000258666800018

    View details for PubMedID 18287579

  • Age-dependent differences in IgG isotype and avidity induced by measles vaccine received during the first year of life JOURNAL OF INFECTIOUS DISEASES Nair, N., Gans, H., Lew-Yasukawa, L., Long-Wagar, A. C., Arvin, A., Griffin, D. E. 2007; 196 (9): 1339-1345

    Abstract

    Measles remains an important cause of death worldwide, and vaccinating individuals at an earlier age could lead to better control of the disease. However, persistence of maternal antibody and young age affect the quantity of vaccine-induced neutralizing antibody and may also affect antibody quality.Enzyme immunoassay was used to analyze measles virus-specific IgG levels, avidity maturation, and isotype changes, using serum samples from infants who received measles vaccine at 6 months of age and measles-mumps-rubella (MMR)-II at 12 months of age (n=26), measles vaccine at 9 months of age and measles-mumps-rubella (MMR)-II at 12 months of age (n=48), or only MMR-II at 12 months of age (n=27).The median IgG level was lower among infants with maternal antibody than among those without maternal antibody. Compared with median avidity indices for infants aged 12 months, median values were lower for 6-month-old infants with maternal antibody (P=.0001), 6-month-old infants without maternal antibody (P=.001), 9-month-old infants with maternal antibody (P=.03), and 9-month-old infants without maternal antibody (P=.006). The median IgG3 level was highest at 6 months of age. IgG1 was predominant at 12 months. Low avidity responses at 6 or 9 months of age did not hinder higher avidity responses or the switch to IgG1 after secondary vaccination. The 2-dose regimen did not augment the response, compared with the response in infants who received 1 dose at 12 months of age.Avidity and isotype maturation of measles vaccine-induced antibody are affected by age, providing insight into the ontogeny of the immune response to measles vaccine.

    View details for DOI 10.1086/522519

    View details for Web of Science ID 000250010800012

    View details for PubMedID 17922398

  • Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Pan, C. H., Valsamakis, A., Colella, T., Nair, N., Adams, R. J., Polack, F. P., Greer, C. E., Perri, S., Polo, J. M., Griffin, D. E. 2005; 102 (33): 11581-11588

    Abstract

    Measles remains a major worldwide problem partly because of difficulties with vaccination of young infants. New vaccine strategies need to be safe and to provide sustained protective immunity. We have developed Sindbis virus replicon particles that express the measles virus (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins. In mice, SIN-H induced high-titered, dose-dependent, MV-neutralizing antibody after a single vaccination. SIN-F, or SIN-H and SIN-F combined, induced somewhat lower responses. To assess protective efficacy, juvenile macaques were vaccinated with a single dose of 10(6) or 10(8) SIN-H particles and infant macaques with two doses of 10(8) particles. A dose of 10(8) particles induced sustained levels of high-titered, MV-neutralizing antibody and IFN-gamma-producing memory T cells, and most monkeys were protected from rash when challenged with wild-type MV 18 months later. After challenge, there was a biphasic appearance of H- and F-specific IFN-gamma-secreting CD4+ and CD8+ T cells in vaccinated monkeys, with peaks approximately 1 and 3-4 months after challenge. Viremia was cleared within 14 days, but MV RNA was detectable for 4-5 months. These studies suggest that complete clearance of MV after infection is a prolonged, phased, and complex process influenced by prior vaccination.

    View details for DOI 10.1073/pnas.0504592102

    View details for Web of Science ID 000231317000005

    View details for PubMedID 16037211

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