Bio

Clinical Focus


  • Pediatric Infectious Disease
  • Infectious Diseases

Academic Appointments


Administrative Appointments


  • Associate Program Director, Stanford/LPCH Pediatric Residency Program (2013 - Present)

Honors & Awards


  • Pfizer Young Investigator Award in Vaccine Development, Infectious Diseases Society of America (2011-2013)
  • MedImmune Career Development Award, Pediatric Infectious Diseases Society (2008-2011)

Professional Education


  • Board Certification: Pediatrics, American Board of Pediatrics (2004)
  • Residency:Lucile Packard Children's Hospital (2004) CA
  • Board Certification: Pediatric Infectious Disease, American Board of Pediatrics (2009)
  • Fellowship, Stanford University, Pediatric Infectious Diseases (2008)
  • Internship:Lucile Packard Children's Hospital (2002) CA
  • Medical Education:Northwestern University Medical School (2001) IL

Research & Scholarship

Current Research and Scholarly Interests


We are interested in developing new therapeutics and vaccines for respiratory viruses such as Influenza and Respiratory Syncytial Virus. We are particularly interested in studying the immune response in children to these viruses and how these responses could be boosted or shaped using novel vaccine adjuvants

Teaching

Graduate and Fellowship Programs


  • Pediatric Infectious Diseases (Fellowship Program)

Publications

Journal Articles


  • Seizure and Meningoencephalitis in an Adolescent CLINICAL PEDIATRICS Li, L., Kay, A. W., Hong, D. K. 2013; 52 (12): 1181-1183

    View details for DOI 10.1177/0009922813506962

    View details for Web of Science ID 000326576300016

    View details for PubMedID 24137030

  • Ruling out bacteremia and bacterial meningitis in infants less than one month of age: is 48 hours of hospitalization necessary? Hospital pediatrics Fielding-Singh, V., Hong, D. K., Harris, S. J., Hamilton, J. R., Schroeder, A. R. 2013; 3 (4): 355-361

    Abstract

    The appropriate duration of hospitalization for infants ≤ 30 days admitted for fever or other concerns for a serious bacterial infection is an understudied area. We sought to determine the risk of a positive, pathogenic bacterial culture of blood or cerebrospinal fluid (CSF) in this population beyond 24 hours after collection.This study was a retrospective review of 1145 infants aged ≤30 days who had a blood or CSF culture from 1999 to 2010 at Santa Clara Valley Medical Center, a county health system in San Jose, California. Time to notification and the probability of a positive culture result after 24 hours were calculated. Infants were considered high risk if they had either a white blood cell count <5000 or >15 000 per µL, a band count >1500 per µL, or an abnormal urinalysis.We identified 1876 cultures (1244 blood, 632 CSF) in 1145 infants aged ≤30 days; 901 (79%) of 1145 were hospitalized and 408 (45%) of 901 hospitalizations were for fever without source (FWS). Thirty-one (2.7%) of the 1145 infants had pathogenic cultures; 6 of 1145 infants (0.5% [95% confidence interval: 0.2-1.1]) had a time to notification >24 hours. All 6 patients had FWS (1.5% of hospitalized FWS sample) and met high-risk criteria on presentation. No low-risk patients had a time to notification >24 hours. Low-risk characteristics were found in 57% (232 of 408) of the entire hospitalized FWS population.Low-risk infants hospitalized for FWS or other concerns for serious bacterial infection may not need hospitalization for a full 48 hours simply to rule out bacteremia and bacterial meningitis.

    View details for DOI 10.1542/hpeds.2013-0009

    View details for PubMedID 24435193

  • Cationic liposome-DNA complexes (CLDC) adjuvant enhances the immunogenicity and cross-protective efficacy of a pre-pandemic influenza A H5N1 vaccine in mice VACCINE Dong, L., Liu, F., Fairman, J., Hong, D. K., Lewis, D. B., Monath, T., Warner, J. F., Belser, J. A., Patel, J., Hancock, K., Katz, J. M., Lu, X. 2012; 30 (2): 254-264

    Abstract

    The development of pre-pandemic influenza A H5N1 vaccines that confer both antigen-sparing and cross-clade protection are a high priority given the limited worldwide capacity for influenza vaccine production, and the antigenic and genetic heterogeneity of circulating H5N1 viruses. The inclusion of potent adjuvants in vaccine formulations may achieve both of these aims. Here we show that the addition of JVRS-100, an adjuvant consisting of cationic liposome-DNA complexes (CLDC) to a clade 1-derived H5N1 split vaccine induced significantly higher virus-specific antibody than unadjuvanted formulations, with a >30-fold dose-sparing effect and induction of increased antigen-specific CD4(+) T-cell responses in mice. All mice that received one dose of adjuvanted vaccine and subsequent H5N1 viral challenges exhibited mild illness, lower lung viral titers, undetectable spleen and brain viral titers, and 100% survival after either homologous clade 1 or heterologous clade 2 H5N1 viral challenges, whereas unadjuvanted vaccine recipients showed significantly increased weight loss, viral titers, and mortality. The protective immunity induced by JVRS-100 adjuvanted H5N1 vaccine was shown to last for over one year without significant waning. Thus, JVRS-100 adjuvanted H5N1 vaccine elicited enhanced humoral and T-cell responses, dose-sparing, and cross-clade protection in mice. CLDC holds promise as an adjuvant for human pre-pandemic inactivated H5N1 vaccines.

    View details for DOI 10.1016/j.vaccine.2011.10.103

    View details for Web of Science ID 000299971800023

    View details for PubMedID 22085545

  • CROSS-REACTIVE NEUTRALIZING ANTIBODY AGAINST PANDEMIC 2009 H1N1 INFLUENZA A VIRUS IN INTRAVENOUS IMMUNOGLOBULIN PREPARATIONS PEDIATRIC INFECTIOUS DISEASE JOURNAL Hong, D. K., Tremoulet, A. H., Burns, J. C., Lewis, D. B. 2011; 30 (1): 67-69

    Abstract

    Prepandemic intravenous immunoglobulin (IVIG) and sera from Kawasaki disease patients treated with this IVIG were analyzed for 2009 H1N1-specific microneutralization and hemagglutination inhibition antibodies. All 6 different IVIG preparations tested had significant levels of cross-reactive-specific antibody at a concentration of 2.0 g/dL of immunoglobulin. Sera from 18 of 19 Kawasaki disease patients had significant increases of cross-reactive-specific antibody after 2.0 g/kg of prepandemic IVIG. These results suggest a role for adjunctive IVIG therapy for severe and/or drug-resistant 2009 H1N1 virus and other highly antigenically drifted influenza strains, particularly in the immunocompromised.

    View details for DOI 10.1097/INF.0b013e3181f127be

    View details for Web of Science ID 000285498800017

    View details for PubMedID 20724956

  • Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity JOURNAL OF VIROLOGY Hong, D. K., Chang, S., Botham, C. M., Giffon, T. D., Fairman, J., Lewis, D. B. 2010; 84 (24): 12691-12702

    Abstract

    Influenza A virus is a negative-strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A virus would induce not only highly robust strain-specific humoral and T-cell immune responses but also cross-protective immunity in which an immune response to antigens from a particular viral subtype (e.g., H3N2) would protect against other viral subtypes (e.g., H1N1). Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/noncoding DNA complexes (CLDC) as adjuvant to whole inactivated influenza A virus vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDC-adjuvanted vaccine induced higher total influenza virus-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multicytokine-producing influenza virus-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted vaccine than with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated influenza virus vaccine.

    View details for DOI 10.1128/JVI.00769-10

    View details for Web of Science ID 000284469600023

    View details for PubMedID 20943978

  • Preferential Lower Respiratory Tract Infection in Swine-Origin 2009 A(H1N1) Influenza CLINICAL INFECTIOUS DISEASES Yeh, E., Luo, R. F., Dyner, L., Hong, D. K., Banaei, N., Baron, E. J., Pinsky, B. A. 2010; 50 (3): 391-394

    Abstract

    We report a case of 2009 influenza A(H1N1) virus infection in which virus was detected predominantly in specimens from the lower respiratory tract but was absent or at very low levels in nasopharyngeal swab samples. This presentation suggests that, in certain hosts or for particular variants of 2009 A(H1N1) virus, the lower respiratory tract may be the preferred site of infection.

    View details for DOI 10.1086/649875

    View details for Web of Science ID 000273500300014

    View details for PubMedID 20047483

  • Cationic lipid/DNA complexes (JVRS-100) combined with influenza vaccine (Fluzone (R)) increases antibody response, cellular immunity, and antigenically drifted protection VACCINE Lay, M., Callejo, B., Chang, S., Hong, D. K., Lewis, D. B., Carroll, T. D., Matzinger, S., Fritts, L., Miller, C. J., Warner, J. F., Liang, L., Fairman, J. 2009; 27 (29): 3811-3820

    Abstract

    Safe and effective adjuvants for influenza vaccines that could increase both the levels of neutralizing antibody, including against drifted viral subtypes, and T-cell immunity would be a major advance in vaccine design. The JVRS-100 adjuvant, consisting of DOTIM/cholesterol cationic liposome-DNA complexes, is particularly promising for vaccines that require induction of high levels of antibody and T-cell immunity, including CD8(+) cytotoxic T lymphocytes (CTL). Inclusion of protein antigens with JVRS-100 results in the induction of enhanced humoral and cell-mediated (i.e., CD4(+) and CD8(+) T cells) immune responses. The JVRS-100 adjuvant combined with a split trivalent influenza vaccine (Fluzone-sanofi pasteur) elicited increased antibody and T-cell responses in mice and non-human primates compared to vaccination with Fluzone alone. Mice vaccinated with JVRS-100-Fluzone and challenged with antigenically drifted strains of H1N1 (PR/8/34) and influenza B (B/Lee/40) viruses had higher grade protection, as measured by attenuation of weight loss and increased survival, compared to recipients of unadjuvanted vaccine. The results indicate that the JVRS-100 adjuvant substantially increases immunogenicity and protection from drifted-strain challenge using an existing influenza vaccine.

    View details for DOI 10.1016/j.vaccine.2009.04.054

    View details for Web of Science ID 000267581300003

    View details for PubMedID 19406188

  • Focus on FOCIS: The continuing diagnostic challenge of autosomal recessive chronic granulomatous disease CLINICAL IMMUNOLOGY Yu, G., Hong, D. K., Dionis, K. Y., Rae, J., Heyworth, P. G., Curnutte, J. T., Lewis, D. B. 2008; 128 (2): 117-126

    Abstract

    Chronic granulomatous disease (CGD) is a primary immunodeficiency of defective neutrophil oxidative burst activity due to mutations in the genes CYBA, NCF-1, NCF-2, and CYBB, which respectively encode the p22-phox, p47-phox, p67-phox, and gp91-phox subunits. CGD usually presents in early childhood with recurrent or severe infection with catalase-positive bacteria and fungi. We present an unusual case of CGD in which Burkholderia cepacia lymphadenitis developed in a previously healthy 10-year-old girl. Flow cytometric analysis of dihydrorhodamine (DHR)-labeled neutrophils performed by a CLIA-approved outside reference laboratory was reported as normal. However, we found that this patient's neutrophil oxidative burst activity in DHR assays was substantially reduced but not absent. A selective decrease in intracellular staining for p67-phox suggested the diagnosis of autosomal recessive CGD due to NCF-2 gene mutations, and a novel homozygous and hypomorphic NCF-2 gene mutation was found. The potential mechanisms for this delayed and mild presentation of CGD are discussed.

    View details for DOI 10.1016/j.clim.2008.05.008

    View details for Web of Science ID 000257941400001

    View details for PubMedID 18625437

  • Liposomal amphotericin B associated with severe hyperphosphatemia PEDIATRIC INFECTIOUS DISEASE JOURNAL Sutherland, S. M., Hong, D. K., Balagtas, J., Gutierrez, K., Dvorak, C. C., Sarwal, M. 2008; 27 (1): 77-79

    Abstract

    We report 4 patients who developed hyperphosphatemia while receiving liposomal amphotericin B to treat an invasive fungal infection. Resolution of the hyperphosphatemia occurred after transition to amphotericin B lipid complex. This phenomenon may occur more commonly in patients with mild to moderate renal insufficiency.

    View details for DOI 10.1097/INF.0b013e31815922a3

    View details for Web of Science ID 000252076200019

    View details for PubMedID 18162947

  • Severe cryptosporidiosis in a seven-year-old renal transplant recipient - Case report and review of the literature PEDIATRIC TRANSPLANTATION Hong, D. K., Wong, C. J., Gutierrez, K. 2007; 11 (1): 94-100

    Abstract

    Cryptosporidium is an intracellular protozoa that can cause gastroenteritis in humans. In immunocompromised hosts, infection can be severe, leading to life-threatening persistent diarrhea. There is limited experience in treating this infection in solid organ transplants. Although newer drugs active against Cryptosporidium exist, they are only licensed in the USA for treatment of immunocompetent hosts. Here we describe a seven-year-old renal transplant recipient with severe cryptosporidiosis. He had a protracted course of diarrhea of up to 2 L/day. He was successfully managed with combination antimicrobial therapy including nitazoxanide, paromomycin, and azithromycin. In conjunction with this regimen, he had a reduction in immunosuppression and complete bowel rest. His stool pattern normalized in four weeks and he has had no recurrence after six months of follow up.

    View details for DOI 10.1111/j.1399-3046.2006.00593.x

    View details for Web of Science ID 000244147500017

    View details for PubMedID 17239130

  • Five-month-old infant with a unilateral pleural effusion PEDIATRIC INFECTIOUS DISEASE JOURNAL Jacobson, L. M., Sikic, N. I., Soslow, J., Hong, D. K., Gutierrez, K., Sectish, T. C. 2007; 26 (2): 189-?
  • Not your routine foreign body: Endobronchial tuberculosis in an infant PEDIATRICS Agarwal, S., Hong, D. K., Soslow, J., Chang, K. W. 2005; 116 (1): 246-248

    Abstract

    Foreign-body aspiration is a common cause of respiratory distress among children. Here we describe an 8-month-old, previously 34-week premature, male patient who presented with a 1-day history of fever and increased work of breathing. Of note, 3 weeks before presentation, the patient had been treated with orally administered amoxicillin for presumed pneumonia and exhibited good clinical response. No chest radiograph was obtained at that time. A current chest radiograph revealed hyperexpansion of the left lung, with a mediastinal shift. Although the patient was referred because of possible foreign-body aspiration, no clear history of an aspiration event was obtained, and computed tomographic scans of the chest were recommended. These showed extensive hilar and mediastinal lymphadenopathy, resulting in obstruction of the left bronchus. Bronchoscopy revealed a cheesy granulomatous mass in the left mainstem bronchus, which was ball-valving into the upper bronchus. Removal resulted in improvement of the patient's respiratory status. Pathology, bronchial lavage, and gastric aspirate specimens all revealed acid-fast bacilli, consistent with Mycobacterium tuberculosis infection. This unusual presentation of tuberculosis may become more common in the United States as the incidence of immigrants carrying tuberculosis increases.

    View details for Web of Science ID 000230207500065

    View details for PubMedID 15995065

  • Blockade of T cell activation using a surface-linked single-chain antibody to CTLA-4 (CD152) JOURNAL OF IMMUNOLOGY Griffin, M. D., Hong, D. K., Holman, P. O., Lee, K. M., Whitters, M. J., O'Herrin, S. M., Fallarino, F., Collins, M., Segal, D. M., Gajewski, T. F., Kranz, D. M., Bluestone, J. A. 2000; 164 (9): 4433-4442

    Abstract

    CTLA-4 (CD152) engagement can down-regulate T cell activation and promote the induction of immune tolerance. However, the strategy of attenuating T cell activation by engaging CTLA-4 has been limited by sharing of its natural ligands with the costimulatory protein CD28. In the present study, a CTLA-4-specific single-chain Ab (scFv) was developed and expressed on the cell surface to promote selective engagement of this regulatory molecule. Transfectants expressing anti-CTLA-4 scFv at their surface bound soluble CTLA-4 but not soluble CD28. Coexpression of anti-CTLA-4 scFv with anti-CD3epsilon and anti-CD28 scFvs on artificial APCs reduced the proliferation and IL-2 production by resting and preactivated bulk T cells as well as CD4+ and CD8+ T cell subsets. Importantly, expression of anti-CTLA-4 scFv on the same cell surface as the TCR ligand was essential for the inhibitory effects of CTLA-4-specific ligation. CTLA-4-mediated inhibition of tyrosine phosphorylation of components of the proximal TCR signaling apparatus was similarly dependent on coexpression of TCR and CTLA-4 ligands on the same surface. These findings support a predominant role for CTLA-4 function in the modification of the proximal TCR signal. Using T cells from DO11.10 and 2C TCR transgenic mice, negative regulatory effects of selective CTLA-4 ligation were also demonstrated during the stimulation of Ag-specific CD4+ and CD8+ T cells by MHC/peptide complexes. Together these studies demonstrate that selective ligation of CTLA-4 using a membrane-bound scFv results in attenuated T cell responses only when coengaged with the TCR during T cell/APC interaction and define an approach to harnessing the immunomodulatory potential of CTLA-4-specific ligation.

    View details for Web of Science ID 000086624300002

    View details for PubMedID 10779742

  • Molecular basis of T cell inactivation by CTLA-4 SCIENCE Lee, K. M., Chuang, E., Griffin, M., Khattri, R., Hong, D. K., Zhang, W. G., Straus, D., Samelson, L. E., Thompson, C. B., Bluestone, J. A. 1998; 282 (5397): 2263-2266

    Abstract

    CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.

    View details for Web of Science ID 000077645800049

    View details for PubMedID 9856951

Conference Proceedings


  • TNF alpha-308A allele in juvenile dermatomyositis - Association with increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications Pachman, L. M., Liota-Davis, M. R., Hong, D. K., Kinsella, T. R., Mendez, E. P., Kinder, J. M., Chen, E. H. WILEY-LISS. 2000: 2368-2377

    Abstract

    To characterize the association between the TNFalpha-308A allele and 1) duration of active disease, 2) peripheral blood mononuclear cell (PBMC) synthesis of tumor necrosis factor alpha (TNFalpha) in vitro, and 3) pathologic calcifications in patients with juvenile dermatomyositis (DM).The TNFalpha-308 alleles were determined by polymerase chain reaction in 37 white patients with juvenile DM and in 29 control subjects. Patients were grouped according to duration of immunosuppressive therapy: long (> or =36 months) or short (<36 months). Unstimulated PBMC were examined by enzyme-linked immunosorbent assay for TNFalpha production in vitro. Sixty-five white patients with juvenile DM were examined for pathologic calcifications.TNFalpha-308A was identified in 18 of 37 patients with juvenile DM, in contrast with 5 of 29 controls (P = 0.009). Sixteen of the 18 patients with juvenile DM who had the TNFalpha-308A allele had a disease course > or =36 months, compared with 6 of 19 patients with TNFalpha-308G (P = 0.001). PBMC from 16 of the 18 juvenile DM patients with TNFalpha-308A synthesized more TNFalpha (median 53 pg/ml) compared with PBMC from 9 of 19 patients with TNFalpha-308G (median 19 pg/ml) (P = 0.007). Nineteen of 22 juvenile DM patients requiring therapy for > or =36 months produced more TNFalpha (median 20.5 pg/ml) in comparison with 6 of 15 juvenile DM patients with a <36-month treatment course (median TNFalpha 0.0 pg/ml) (P = 0.005). Detectable calcifications were present in 3 of 8 children with juvenile DM who had TNFalpha-308AA, compared with 2 of 21 children with TNFalpha-308AG and 1 of 36 children who had TNFalpha-308GG (P = 0.017).A long course of juvenile DM and the presence of pathologic calcifications were associated with the TNFalpha-308A allele and with the increased production of TNFalpha, which may perpetuate the inflammatory response.

    View details for Web of Science ID 000089757900026

    View details for PubMedID 11037898

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