Vaccines, Blood & Biologics
HIV, Influenza, and Smallpox Vaccines: Development of New Assays and Animal Models for Evaluation of Vaccine Safety and Efficacy
Principal Investigator: H. Golding, PhD
Office / Division / Lab: OVRR / DVP / LR
Industry and academic researchers are developing new vaccines against viruses, including HIV, pandemic influenza strains such as H1N1 (swine influenza) and H5N1 (avian influenza), and the smallpox virus. Some of these vaccines are being developed to work with new types of adjuvants (agents that stimulate or increase immune response to vaccines).
Therefore, in addition to evaluating the safety and efficacy of the vaccine itself, FDA also must evaluate the combination of vaccine and its adjuvant. Moreover, evaluation of each viral vaccine presents unique challenges that agency regulators must address individually.
The goal of our program is to develop new and improved tools for monitoring vaccine safety and efficacy. FDA will then share these new tools with the regulated industry to enable use of these tools in their research and development efforts.
The availability of new tools could reduce the time it takes to develop new vaccines against HIV, influenza, and smallpox, and help FDA to recognize quickly potential safety problems with vaccines that use new adjuvants. Thus, our work will contribute significantly to public health in the US and globally by facilitating development and approval of new vaccines that prevent serious diseases.
Our laboratory is working to generate effective vaccines against highly pathogenic avian influenza (H5N1), and against the newly emerging swine influenza H1N1.
Future vaccines for influenza strains with pandemic potential will likely be combined with adjuvants in order to improve their immunogenicity, to generate heterosubtypic neutralizing activity, and to reduce the amount of antigen required for vaccination--an important advantage for global vaccination campaigns.
In parallel with vaccine development, we are working to improve the analytical tools available for comparing immune responses generated by different vaccine candidates. Therefore, our laboratory initiated the use of whole genome phage display libraries to screen antibody repertoires, and surface plasmon resonance to measure antibody binding to properly folded, large HA1 fragments. Both tools are used to screen convalescent sera, monoclonal antibodies, and to compare sera from recipients of unadjuvanted vaccines with that of recipients of adjuvanted vaccines.
Many of these new adjuvants contain components that can cause unacceptable reactogenicity and systemic adverse reactions. Often these adverse reactions are undetectable in pre-clinical toxicity studies in small animals due to species differences in the cellular receptor targeted by the novel adjuvants or because of their relative sensitivity to drug-associated toxicities. Therefore, we are developing rapid in vitro screening assays based on human cells to evaluate the activity of new adjuvants and to identify parameters that will predict unacceptable toxicities during in vivo studies.
Another major goal of our program is to resolve a problem facing investigators running HIV vaccine clinical trials. Participants of these vaccine trials are not infected. However, most HIV-1 prophylactic vaccines under development are complex products containing multiple HIV genes or proteins. As a result, the sera of vaccine recipient are expected to be reactive in licensed HIV-1 detection kits. Thus, HIV-negative individuals who have received an investigative vaccine will be erroneously identified as being HIV-positive. This will likely complicate future phase III efficacy trials of prophylactic HIV vaccines that require early detection of breakthrough infections. Therefore, our laboratory developed HIV-SELECTEST (both a serodiagnostic EIA and the Multispot Rapid Test) that provides differential diagnosis of true HIV infection in the presence of vaccine-induced antibodies. Both versions of the test are in advance stages of development and transfer to the National Heart Blood and Lung Institute for production and licensure.
Our program is also supporting development of safer smallpox vaccines. The development of novel vaccines against smallpox and of new pre- or post-exposure therapies is critically dependent on pre-clinical testing in animal models. Various endpoints are used to follow infections in mice, including weight loss, pox lesion scoring, and lethality. These endpoints are not optimal since they cannot avoid morbidity, nor can they accurately predict lethality in individual animals. In response to this limitation we established whole-body bioimaging of animals challenged with recombinant vaccinia-luciferase. This new approach, in addition to the use of advanced statistic tools, will provide a practical, quantitative, and humane approach to following virus dissemination in animal models and for evaluating the efficacy of novel vaccines and therapies for smallpox.
PLoS One 2015 Jan 28;10(1):e0115476
Oral Priming with Replicating Adenovirus Serotype 4 Followed by Subunit H5N1 Vaccine Boost Promotes Antibody Affinity Maturation and Expands H5N1 Cross-Clade Neutralization.
Khurana S, Coyle EM, Manischewitz J, King LR, Ishioka G, Alexander J, Smith J, Gurwith M, Golding H
J Infect Dis 2014 Jun 15;209(12):1860-9
A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response.
Talaat KR, Luke CJ, Khurana S, Manischewitz J, King LR, McMahon BA, Karron RA, Lewis KD, Qin J, Follmann DA, Golding H, Neuzil KM, Subbarao K
Cell 2014 Apr 10;157(2):499-513
Global analyses of human immune variation reveal baseline predictors of postvaccination responses.
Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z, Germain RN, Wang E, Olnes MJ, Narayanan M, Golding H, Moir S, Dickler HB, Perl S, Cheung F, Baylor HIPC Center, CHI Consortium
PLoS One 2014 Apr 22;9(4):e95496
Heterologous prime-boost vaccination with MF59-adjuvanted H5 vaccines promotes antibody affinity maturation towards the hemagglutinin HA1 domain and broad H5N1 cross-clade neutralization.
Khurana S, Coyle EM, Dimitrova M, Castellino F, Nicholson K, Giudice GD, Golding H
Vaccine 2014 Apr 17;32(19):2188-97
Novel antibody-independent receptor-binding SPR-based assay for rapid measurement of influenza vaccine potency.
Khurana S, King LR, Manischewitz J, Coyle EM, Golding H
Biologicals 2013 Nov;41(6):458-68
Predictive markers of safety and immunogenicity of adjuvanted vaccines.
Mastelic B, Garcon N, Del Giudice G, Golding H, Gruber M, Neels P, Fritzell B
J Virol 2013 Sep;87(17):9742-53
Influenza a virus hemagglutinin trimerization completes monomer folding and antigenicity.
Magadán JG, Khurana S, Das SR, Frank GM, Stevens J, Golding H, Bennink JR, Yewdell JW
J Infect Dis 2013 Aug;208(3):413-7
DNA priming prior to H5N1 inactivated influenza vaccination expands antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults.
Khurana S, Wu J, Dimitrova M, King LR, Manischewitz J, Graham BS, Ledgerwood JE, Golding H
Vaccine 2013 Aug 20;31(37):3987-94
Development of a simple, rapid, sensitive, high-throughput luciferase reporter based microneutralization test for measurement of virus neutralizing antibodies following respiratory syncytial virus vaccination and infection.
Fuentes S, Crim RL, Beeler J, Teng MN, Golding H, Khurana S
Sci Transl Med 2013 Aug 28;5(200):200ra114
Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.
Khurana S, Loving CL, Manischewitz J, King LR, Gauger PC, Henningson J, Vincent AL, Golding H
Vaccine 2013 Jul 11;31(32):3209-21
Strengthening the influenza vaccine virus selection and development process: Outcome of the 2nd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at the Centre International de Conferences (CICG) Geneva, Switzerland, 7 to 9 December 2011.
Al Busaidy S, Al-Gohary A, Ampofo WK, Bekshin Z, Cerkaoui I, Claes F, Cox NJ, Cracknell W, Cui L, Paiva TM, de Wit M, Diep LDT, Donabedian A, Donis R, Dormitzer PR, Eichelberger M, El Kholy N, Engelhardt O, Engelmann HB, Eropkin MY, Fasce R, Fontaine L, Ghadakchi HF, Ghedin E, Giovanni MY, Golding H, da Silva HC, Gysin R, Hamilton K, Hauge SH, Hay A, Huang S, Hungnes O, Ibrahim SSS, Immamura T, Inglis SC, Kadjo H, Katz J, Kawaoka Y, Kelso A, Khan MI, Kilander A, Klimov A, Kreij K, Kusmiaty D, Linde A, Liu MT, Lupulescu E, Mai LQ, Martinez VR, McCauley J, Meyer Q, Modi R, Mohammadi AA, Mokhtari-Azad T, Mol E, Music T, Nelson K, Neuhaus E, Neumeier ER, Niang MN, Odagiri T, Peiris M, Pohlmann A, Popow-Kraupp T, Trilar KP, Rabadan R, Rambaut A, Robertson JS, Rolls C, Sampurno OD, Savy V, Sawanpanyaltert P, Schmid G, Schweiger B, Shapira S, Shinde V, Shu Y, Siqueira M, Smith D, Spiro D, Stevens J, Takizawa K, Tashiro M, Taylor B, Thomas Y, Tsai T, Van der Werf S, Venter M, Waddell AL, Wan XF, Wang D, Webby R, Weir JP, Wentworth D, Wickramasinghe G, Ye ZP, Zambon M, Ziegler T
Sci Transl Med 2013 Jun 26;5(191):191ed8
Getting to the heart of influenza.
Yewdell JW, Spiro DJ, Golding H, Quill H, Mittelman A, Nabel GJ
J Virol 2013 May;87(10):5564-76
Effects of post-challenge administration of ST-246 on dissemination of IHD-J-Luc vaccinia virus in normal and in immune deficient mice reconstituted with T cells.
Zaitseva M, Shotwell E, Scott J, Cruz S, King LR, Manischewitz J, Diaz CG, Jordan R, Grosenbach D, Golding H
Biologicals 2013 Mar;41(2):115-24
Potential use of inflammation and early immunological event biomarkers in assessing vaccine safety.
Mastelic B, Lewis DJ, Golding H, Gust I, Sheets R, Lambert PH
J Infect Dis 2013 Jan;207(2):288-96
Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine.
He XS, Sasaki S, Baer J, Khurana S, Golding H, Treanor JJ, Topham DJ, Sangster MY, Jin H, Dekker CL, Subbarao K, Greenberg HB
Proc Natl Acad Sci U S A 2013 Jan 2;110(1):264-9
Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.
Schmidt AG, Xu H, Khan AR, O'Donnell T, Khurana S, King LR, Manischewitz J, Golding H, Suphaphiphat P, Carfi A, Settembre EC, Dormitzer PR, Kepler TB, Zhang R, Moody MA, Haynes BF, Liao HX, Shaw DE, Harrison SC
J Virol 2012 Nov;86(22):12283-93
Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild type H5N1 influenza challenge and control viral loads better than subunit H5N1 vaccine by eliciting high affinity antibodies.
Verma S, Dimtrova M, Munjal A, Fontana J, Crevar CJ, Carter DM, Ross TM, Khurana S, Golding H
PLoS Pathog 2012 Sep;8(9):e1002920
AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans.
Khurana S, Frasca D, Blomberg B, Golding H
Vaccine 2012 Jul 6;30(32):4859-65
159-Use of human MonoMac6 cells for development of in vitro assay predictive of adjuvant safety in vivo.
Zaitseva M, Romantseva T, Blinova K, Beren J, Sirota L, Drane D, Golding H
Methods Mol Biol 2012;890:161-76
Measurements of vaccinia virus dissemination using whole body imaging: approaches for predicting of lethality in challenge models and testing of vaccines and antiviral treatments.
Zaitseva M, Kapnick S, Golding H
J Virol 2012 May;86(10):5515-22
Influenza virus H1N1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (HA1 Domain) in the elderly than in young adults and children.
Verma N, Dimitrova M, Carter DM, Crevar CJ, Ross TM, Golding H, Khurana S
J Infect Dis 2012 Feb;205(4):610-20
Immune response following H1N1pdm09 vaccination: differences in antibody repertoire and avidity in young adults and elderly populations stratified by age and gender.
Khurana S, Verma N, Talaat KR, Karron RA, Golding H
J Virol 2011 Dec;85(23):12455-63
H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.
Khurana S, Sasono P, Fox A, Kinh NV, Mai LQ, Thai PQ, Hien NT, Liem NT, Horby P, Golding H
J Virol 2011 Nov;85(21):10945-54
H5N1 virus-like particle vaccine elicits cross-reactive neutralizing antibodies in humans that preferentially bind to oligomeric form of influenza hemagglutinin.
Khurana S, Wu J, Verma N, Verma S, Raghunandan R, Manischewitz J, King LR, Kpamegan E, Pincus S, Smith G, Glenn G, Golding H
J Virol 2011 Sep;85(17):9147-58
Passive immunotherapies protect WRvFire and IHD-J-Luc vaccinia virus infected mice from lethality by reducing viral loads in the upper respiratory tract and internal organs.
Zaitseva M, Kapnick SM, Meseda CA, Shotwell E, King LR, Manischewitz J, Scott J, Kodihalli S, Merchlinsky M, Nielsen H, Lantto J, Weir JP, Golding H
Vaccine 2011 Aug 5;29(34):5657-65
Recombinant HA1 produced in E. coli forms functional oligomers and generates strain-specific SRID potency antibodies for pandemic influenza vaccines.
Khurana S, Larkin C, Verma S, Joshi MB, Fontana J, Steven AC, King LR, Manischewitz J, McCormick W, Gupta RK, Golding H
Proc Natl Acad Sci U S A 2011 Aug 23;108(34):14216-21
Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin.
Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, Golding H, Dormitzer PR, Haynes BF, Walter EB, Moody MA, Kepler TB, Liao HX, Harrison SC
Sci Transl Med 2011 Jun 1;3(85):85ra48
MF59 adjuvant enhances diversity and affinity of antibody-mediated immune response to pandemic influenza vaccines.
Khurana S, Verma N, Yewdell JW, Hilbert AK, Castellino F, Lattanzi M, Del Giudice G, Rappuoli R, Golding H
J Virol 2011 Feb;85(3):1246-56
Bacterial HA1 vaccine against pandemic H5N1 influenza: evidence of oligomerization, hemagglutination, and cross- protective immunity in ferrets.
Khurana S, Verma S, Verma N, Crevar CJ, Carter DM, Manischewitz J, King LR, Ross TM, Golding H
PLoS One 2011 Feb 28;6(2):e17297
A rapid Flp-In system for expression of secreted H5N1 influenza hemagglutinin vaccine immunogen in mammalian cells.
Lu H, Khurana S, Verma N, Manischewitz J, King L, Beigel JH, Golding H
Immunol Rev 2011 Jan;239(1):167-77
Influenza vaccine immunology.
Dormitzer PR, Galli G, Castellino F, Golding H, Khurana S, Del Giudice G, Rappuoli R
FASEB J 2011 Jan;25(1):55-65
Receptor activity modifying protein-3 mediates the protumorigenic activity of lysyl oxidase-like protein-2.
Brekhman V, Lugassie J, Zaffryar-Eilot S, Sabo E, Kessler O, Smith V, Golding H, Neufeld G
PLoS One 2010 Jul 12;5(7):e11548
Properly folded bacterially expressed H1N1 hemagglutinin globular head and ectodomain vaccines protect ferrets against H1N1 pandemic influenza virus.
Khurana S, Verma S, Verma N, Crevar CJ, Carter DM, Manischewitz J, King LR, Ross TM, Golding H
Vaccine 2010 Jan 8;28(3):790-7
A practical influenza neutralization assay to simultaneously quantify hemagglutinin and neuraminidase-inhibiting antibody responses.
Hassantoufighi A, Zhang H, Sandbulte M, Gao J, Manischewitz J, King L, Golding H, Straight TM, Eichelberger MC
J Clin Microbiol 2010 Jan;48(1):281-5
HIV-Selectest enzyme immunoassay and rapid test: ability to detect seroconversion following HIV-1 infection.
Khurana S, Norris PJ, Busch MP, Haynes BF, Park S, Sasono P, Mlisana K, Salim AK, Hecht FM, Mulenga J, Chomba E, Hunter E, Allen S, Nemo G, Rodriguez-Chavez IR, Women's Interagency HIV Study, Joseph B. Margolick on behalf of Multicenter AIDS Cohort Study (MACS), Golding H
Sci Transl Med 2010 Jan 20;2(15):15ra5
Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus.
Khurana S, Chearwae W, Castellino F, Manischewitz J, King LR, Honorkiewicz A, Rock MT, Edwards KM, Del Giudice G, Rappuoli R, Golding H
J Virol 2009 Oct;83(20):10437-47
Application of bioluminescence imaging to the prediction of lethality in vaccinia virus infected mice.
Zaitseva M, Kapnick SM, Scott J, King LR, Manischewitz J, Sirota L, Kodihalli S, Golding H
Clin Vaccine Immunol 2009 Aug;16(8):1105-12
Statistical approach to estimate vaccinia-specific neutralizing antibody titers using a high throughput assay.
Kennedy R, Pankratz VS, Swanson E, Watson D, Golding H, Poland GA
Proc Natl Acad Sci U S A 2009 Aug 17;106(35):14802-7
Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production.
Chu C, Lugovtsev V, Golding H, Betenbaugh M, Shiloach J
J Virol 2009 May;83(9):4624-30
Electroporation of Synthetic DNA Antigens Offers Protection in Non-Human Primates Challenged with Highly Pathogenic Avian Influenza.
Laddy DJ, Yan J, Khan AS, Anderson H, Cohn A, Greenhouse J, Lewis M, Manischewitz J, King LR, Golding H, Draghia-Akli R, Weiner DB
PLoS Med 2009 Apr 21;6(4):e1000049
Antigenic fingerprinting of H5N1 avian influenza using convalescent sera and monoclonal antibodies reveals potential vaccine and diagnostic targets.
Khurana S, Suguitan AL Jr, Rivera Y, Simmons CP, Lanzavecchia A, Sallusto F, Manischewitz J, King LR, Subbarao K, Golding H
Vaccine 2008 Aug 12;26(34):4299-303
FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007.
Eichelberger M, Golding H, Hess M, Weir J, Subbarao K, Luke CJ, Friede M, Wood D
Int Immunol 2007 Nov;19(11):1249-60
Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc, and Tcf3 transcription factors in the thymic stroma
Popa I, Zubkova I, Medvedovic M, Romantseva T, Mostowski H, Boyd R, Zaitseva M
J Infect Dis 2007 Oct 1;196(7):1026-32
Antibodies to the A27 Protein of Vaccinia Virus Neutralize and Protect against Infection but Represent a Minor Component of Dryvax Vaccine-Induced Immunity.
He Y, Manischewitz J, Meseda CA, Merchlinsky M, Vassell RA, Sirota L, Berkower I, Golding H, Weiss CD
AIDS 2007 Feb 19;21(4):521-4
Durable neutralizing antibodies after remote smallpox vaccination among adults with and without HIV infection.
Kan VL, Manischewitz J, King LR, Golding H
J Acquir Immune Defic Syndr 2006 Nov 1;43(3):304-12
Novel Approach for Differential Diagnosis of HIV Infections in the Face of Vaccine-Generated Antibodies: Utility for Detection of Diverse HIV-1 Subtypes.
Khurana S, Needham J, Park S, Mathieson B, Busch MP, Nemo G, Nyambi P, Zolla-Pazner S, Laal S, Mulenga J, Chomba E, Hunter E, Allen S, McIntyre J, Hewlett I, Lee S, Tang S, Cowan E, Beyrer C, Altfeld M, Yu XG, Tounkara A, Koita O, Kamali A, Nguyen N, Graham BS, Todd D, Mugenyi P, Anzala O, Sanders E, Ketter N, Fast P, Golding H
J Immunol 2006 Aug 15;177(4):2552-64
Subunit recombinant vaccine protects against monkeypox.
Heraud JM, Edghill-Smith Y, Ayala V, Kalisz I, Parrino J, Kalyanaraman VS, Manischewitz J, King LR, Hryniewicz A, Trindade CJ, Hassett M, Tsai WP, Venzon D, Nalca A, Vaccari M, Silvera P, Bray M, Graham BS, Golding H, Hooper JW, Franchini G
J Virol 2006 Mar;80(5):2092-9
Human Immunodeficiency Virus (HIV) Vaccine Trials: a Novel Assay for Differential Diagnosis of HIV Infections in the Face of Vaccine-Generated Antibodies.
Khurana S, Needham J, Mathieson B, Rodriguez-Chavez IR, Catanzaro AT, Bailer RT, Kim J, Polonis V, Cooper DA, Guerin J, Peterson ML, Gurwith M, Nguyen N, Graham BS, Golding H
Clin Infect Dis 2006 Feb 15;42(4):e16-20
Clinical and immunological comparison of smallpox vaccine administered to the outer versus the inner upper arms of vaccinia-naive adults.
Waibel KH, Golding H, Manischewitz J, King LR, Tuchscherer M, Topolski RL, Walsh DS
J Leukoc Biol 2005 Dec;78(6):1306-17
Increased CXCR4-dependent HIV-1 fusion in activated T cells: role of CD4/CXCR4 association.
Zaitseva M, Romantseva T, Manischewitz J, Wang J, Goucher D, Golding H
Virology 2005 Sep 1;339(2):164-75
Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model.
Meseda CA, Garcia AD, Kumar A, Mayer AE, Manischewitz J, King LR, Golding H, Merchlinsky M, Weir JP
J Biol Chem 2005 Aug 19;280(33):29570-7
CCR5 N-terminal region plays a critical role in HIV-1 inhibition by toxoplasma gondii derived cyclophilin-18.
Golding H, Khurana S, Yarovinsky F, King LR, Abdoulaeva G, Antonsson L, Owman C, Platt EJ, Kabat D, Andersen JF, Sher A
Nat Med 2005 Jul;11(7):740-7
Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus.
Edghill-Smith Y, Golding H, Manischewitz J, King LR, Scott D, Bray M, Nalca A, Hooper JW, Whitehouse CA, Schmitz JE, Reimann KA, Franchini G
J Virol 2005 Jun;79(11):6791-800
Identification of a Linear Peptide Recognized by Monoclonal Antibody 2D7 Capable of Generating CCR5-Specific Antibodies with Human Immunodeficiency Virus-Neutralizing Activity.
Khurana S, Kennedy M, King LR, Golding H
Biotechnol Bioeng 2005 Jun 20;90(6):663-74
Production of recombinant proteins by vaccinia virus in a microcarrier based mammalian cell perfusion bioreactor.
Bleckwenn NA, Golding H, Bentley WE, Shiloach J
J Infect Dis 2005 Feb 1;191(3):372-81
Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.
Edghill-Smith Y, Bray M, Whitehouse CA, Miller D, Mucker E, Manischewitz J, King LR, Robert-Guroff M, Hryniewicz A, Venzon D, Meseda C, Weir J, Nalca A, Livingston V, Wells J, Lewis MG, Huggins J, Zwiers SH, Golding H, Franchini G.
J Biol Chem 2004 Dec 17;279(51):53635-42
Structural determinants of the anti-HIV activity of a CCR5 antagonist derived from Toxoplasma gondii.
Yarovinsky F, Andersen JF, King LR, Caspar P, Aliberti J, Golding H, Sher A
J Med Primatol 2004 Aug;33(4):167-74
Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus.
Eller N, Golding H, Inoue S, Beining P, Inman J, Matthews N, Scott DE, Golding B
Vox Sang 2004 Feb;86(2):125-9
Intravenous immunoglobulin products contain neutralizing antibodies to vaccinia.
Goldsmith JC, Eller N, Mikolajczyk M, Manischewitz J, Golding H, Scott DE