Longitudinal and Functional Analysis of Spontaneous NY-ESO-1-Specific Antibody Responses in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2831-2831
Author(s):  
Sebastian Kobold ◽  
Yanran Cao ◽  
Sinje Tams ◽  
Britta Marlen Bartels ◽  
Tim Lütkens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Plasma Samples ◽  
Specific Antibodies ◽  
Functional Capabilities ◽  
Bone Marrow Plasma ◽  
Ct Antigen ◽  
Antibody Titers

Abstract Abstract 2831 Poster Board II-807 Its tumor-restricted expression and its high immunogenicity render cancer-testis (CT) antigen NY-ESO-1 an exquisite target for antigen-specific immunotherapies. Spontaneous antibody responses against NY-ESO-1 are typically found in a subset of patients with solid tumors. However, little is known regarding serological immune responses against NY-ESO-1 in patients with hematological malignancies including multiple myeloma (MM). Furthermore, no consequent longitudinal analyses have been performed correlating NY-ESO-1-specific antibody titers with the clinical development of the given malignancy. Finally, nothing is known regarding the functional capabilities of spontaneously occurring anti-NY-ESO-1 antibodies in MM or other malignancies. Here, we performed the first longitudinal and functional investigation of NY-ESO-1-specific antibody responses in MM analyzing 1100 sera and 200 bone marrow plasma samples of 194 MM patients. Sera and BM plasma samples of 100 healthy donors served as controls. Screening sera and bone marrow plasma of our MM patients by Enzyme-linked Immunosorbent Assay (ELISA) using full length recombinant NY-ESO-1 protein, we found that 5/194 patients had high-titered antibody responses against this CT antigen. A quantitative B cell ELISPOT demonstrated NY-ESO-1-specific B cells in the peripheral blood as well as in the bone marrow of the respective MM patients. In a western blot analysis, spontaneous NY-ESO-1-specific immune responses in the patients were found to be highly specific for both native and recombinant protein. Epitope mapping in an ELISA using 18 overlapping NY-ESO-1 20mer peptides showed that antibody responses were restricted to the first 70 amino acids of the full-length protein. NY-ESO-1-specific antibodies consisted mainly of IgG1 and to a lower extent of IgG3 subtypes. No IgG2, IgG4, IgM or IgA antibodies against NY-ESO-1 were detected. Interestingly, antibody affinity increased over the course of the disease suggesting an affinity driven antibody maturation. Accordingly, NY-ESO-1-specific antibodies of MM patients were found to be potent complement activators in a western blot technique. On the other hand, despite the high functional capabilities of NY-ESO-1-specific antibodies, antibody titers increased with each NY-ESO-1-expressing (as indicated by reverse-transcriptase-polymerase-chain-reaction and immunohistochemistry) recurrence of the disease. In conclusion, we demonstrate here the spontaneous occurrence of high-titered NY-ESO-1-specific antibodies in MM patients. One reason for the relatively low frequency of antibody responses against NY-ESO-1 might be that most patients were in early stages of the disease or in remission at the time the analysis was performed. Antibodies were produced by NY-ESO-1-specific B cells detectable in the bone marrow as well as in the peripheral blood of the patients. NY-ESO-1-specific antibodies were evoked by a distinct and immunodominant fragment of NY-ESO-1. Affinity maturation of this response and complement activation by the spontaneously occurring NY-ESO-1-specific IgG1-type antibodies speak in favour of an effective serological immune response. However, positive correlation of antibody titers with tumor burden and recurrence of the disease suggest an inability of antibodies targeting intracellular protein NY-ESO-1 to control the course of the disease, at least in the long run. Antigen-specific immunotherapy might be necessary to shape NY-ESO-1-specific immunity in MM patients and, particularly, to mobilize tumor-specific T cell responses. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Development and validation of an assay for detection of Japanese Encephalitis virus specific antibody responses

2020 ◽  
Author(s):  
Pradeep Darshana Pushpakumara ◽  
Chandima Jeewandara ◽  
Laksiri Gomes ◽  
Yashodha Perera ◽  
Ananda Wijewickrama ◽  
...  
Keyword(s):  
Immune Responses ◽  
Japanese Encephalitis Virus ◽  
Disease Severity ◽  
Japanese Encephalitis ◽  
Specific Antibody ◽  
Encephalitis Virus ◽  
Antibody Responses ◽  
Specific Antibodies ◽  
Dengue Disease ◽  
Conserved Regions

AbstractBackgroundAlthough immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity.Methodology/Principal findings20 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N=30), those who were only immune to the JEV and not DENV (JEV+DENV-, N=30), those who were only immune to DENV(JEV-DENV+, N=30) and in those who were immune to both viruses (JEV+DENV+, N=30). 7/20 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV-and 30/30 JEV+DENV+individuals, and only 3/30 (10%) JEV-DENV+individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n=175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n=175) (OR 5.3, 95% CI 3.3 to 8.3).Conclusions/SignificanceAs our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.Author summaryBoth Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) co-circulate in the same geographical region and have a potential to modulate the immune responses to each other. However, due to the difficulty in identifying antibody responses specific to either virus due to the highly cross-reactive nature of virus-specific antibodies, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV-specific, DENV non cross-reactive antibody responses by identifying JEV-specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV-specific antibodies associates with dengue disease severity. 20 JEV-specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed. We found that seven peptides were highly immunogenic and specific to the JEV and we further evaluated the usefulness of an ELISA developed using these pools of peptides. We found that our in-house ELISA was found to be significantly more sensitive some of the existing commercial assays. As this assay appears to be highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.

scholarly journals Repeated Influenza Vaccination Boosts and Maintains H1N1pdm09 Neuraminidase Antibody Titers

2021 ◽  
Vol 12 ◽  
Author(s):  
Lena Hansen ◽  
Fan Zhou ◽  
Håkon Amdam ◽  
Mai-Chi Trieu ◽  
Rebecca Jane Cox
Keyword(s):  
Specific Antibody ◽  
Seroconversion Rate ◽  
Geometric Mean ◽  
Surface Protein ◽  
Fold Increase ◽  
Antibody Responses ◽  
Influenza Vaccines ◽  
Specific Antibodies ◽  
Antibody Titers ◽  
Functional Antibodies

Antibodies to influenza surface protein neuraminidase (NA) have been found to reduce disease severity and may be an independent correlate of protection. Despite this, current influenza vaccines have no regulatory requirements for the quality or quantity of the NA antigen and are not optimized for induction of NA-specific antibodies. Here we investigate the induction and durability of NA-specific antibody titers after pandemic AS03-adjuvanted monovalent H1N1 vaccination and subsequent annual vaccination in health care workers in a five-year longitudinal study. NA-specific antibodies were measured by endpoint ELISA and functional antibodies measured by enzyme-linked lectin assay (ELLA) and plaque reduction naturalisation assay. We found robust induction of NA inhibition (NAI) titers with a 53% seroconversion rate (&gt;4-fold) after pandemic vaccination in 2009. Furthermore, the endpoint and NAI geometric mean titers persisted above pre-vaccination levels up to five years after vaccination in HCWs that only received the pandemic vaccine, which demonstrates considerable durability. Vaccination with non-adjuvanted trivalent influenza vaccines (TIV) in subsequent influenza seasons 2010/2011 – 2013/2014 further boosted NA-specific antibody responses. We found that each subsequent vaccination increased durable endpoint titers and contributed to maintaining the durability of functional antibody titers. Although the trivalent influenza vaccines boosted NA-specific antibodies, the magnitude of fold-increase at day 21 declined with repeated vaccination, particularly for functional antibody titers. High levels of pre-existing antibodies were associated with lower fold-induction in repeatedly vaccinated HCWs. In summary, our results show that durable NA-specific antibody responses can be induced by an adjuvanted influenza vaccine, which can be maintained and further boosted by TIVs. Although NA-specific antibody responses are boosted by annual influenza vaccines, high pre-existing titers may negatively affect the magnitude of fold-increase in repeatedly vaccinated individuals. Our results support continued development and standardization of the NA antigen to supplement current influenza vaccines and reduce the burden of morbidity and mortality.

scholarly journals Simultaneous Immunization with Multiple Diverse Immunogens Alters Development of Antigen-Specific Antibody-Mediated Immunity

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 964
Author(s):  
Kelsey A. Pilewski ◽  
Kevin J. Kramer ◽  
Ivelin S. Georgiev
Keyword(s):  
Specific Antibody ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Emerging Pathogens ◽  
Igg Antibody ◽  
Neisseria Meningitides ◽  
Immunization Strategies ◽  
Single Antigen ◽  
The Face ◽  
Antibody Titers

Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic Escherichia coli, Mycobacterium tuberculosis, and Neisseria meningitides, and monitored the development of antigen-specific IgG antibody responses. We found that antigen-specific endpoint antibody titers were comparable across immunization groups by study conclusion (day 70). Further, we discovered that although cocktail-immunized mice initially elicited more robust antibody responses, the rate of titer development decreases significantly over time compared to single antigen-immunized mice. Investigating the basic properties that govern the development of antigen-specific antibody responses will help inform the design of future combination immunization regimens.

scholarly journals Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

2015 ◽  
Vol 194 (6) ◽  
pp. 2561-2568 ◽  
Author(s):  
Jairo M. Montezuma-Rusca ◽  
Susan Moir ◽  
Lela Kardava ◽  
Clarisa M. Buckner ◽  
Aaron Louie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cells ◽  
Primary Source ◽  
Specific Antibodies ◽  
Bone Marrow Plasma ◽  
Hiv 1

scholarly journals Complement receptors regulate differentiation of bone marrow plasma cell precursors expressing transcription factors Blimp-1 and XBP-1

2005 ◽  
Vol 201 (6) ◽  
pp. 993-1005 ◽  
Author(s):  
Dominique Gatto ◽  
Thomas Pfister ◽  
Andrea Jegerlehner ◽  
Stephen W. Martin ◽  
Manfred Kopf ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Plasma Cell ◽  
Cell Activation ◽  
Plasma Cells ◽  
Antibody Responses ◽  
Complement Receptors ◽  
Essentially Normal ◽  
Bone Marrow Plasma

Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21–CD19–CD81 coreceptor complex into the B cell antigen receptor (BCR) complex, which lowers the threshold of B cell activation and increases the survival and proliferative capacity of responding B cells. To investigate the role of the CD21–CD35 complement receptors in the generation of B cell memory, we analyzed the response against viral particles derived from the bacteriophage Qβ in mice deficient in CD21–CD35 (Cr2−/−). Despite highly efficient induction of early antibody responses and germinal center (GC) reactions to immunization with Qβ, Cr2−/− mice exhibited impaired antibody persistence paralleled by a strongly reduced development of bone marrow plasma cells. Surprisingly, antigen-specific memory B cells were essentially normal in these mice. In the absence of CD21-mediated costimulation, Qβ-specific post-GC B cells failed to induce the transcriptional regulators Blimp-1 and XBP-1 driving plasma cell differentiation, and the antiapoptotic protein Bcl-2, which resulted in failure to generate the precursor population of long-lived plasma cells residing in the bone marrow. These results suggest that complement receptors maintain antibody responses by delivery of differentiation and survival signals to precursors of bone marrow plasma cells.

scholarly journals Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies

2015 ◽  
Vol 90 (2) ◽  
pp. 1116-1128 ◽  
Author(s):  
Greg A. Kirchenbaum ◽  
Donald M. Carter ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Receptor Binding ◽  
Specific Antibody ◽  
H1n1 Virus ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Specific Antibodies ◽  
Antibody Titers ◽  
Sequential Infection ◽  
Virus Isolates

ABSTRACTBroadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus.IMPORTANCEThe influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses directed at the HA stalk region. Moreover, ferrets possessing HA stalk-specific antibody were protected against novel H1N1 virus infection and did not transmit the virus to naive contacts.

Strong Antibody Responses Against a Unique Region of CT-Antigen SSX-2 Are Induced After Allogeneic Stem Cell Transplantation and Correlate with Clinical Remission In Patients with Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1900-1900
Author(s):  
Sebastian Kobold ◽  
Tim Luetkens ◽  
Yanran Cao ◽  
Corinna Eberhardt ◽  
Sinje Tams ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Immune Responses ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Antibody Responses ◽  
Unique Region ◽  
Ct Antigen

Abstract Abstract 1900 Cancer-testis (CT) antigens show an expression restricted to malignancies and the human germline among healthy tissues and, therefore, represent attractive targets for cancer vaccines. CT antigen SSX-2 is expressed in about 20% of multiple myeloma patients (MM), however, little is known about the occurrence of spontaneous humoral immune responses against SSX-2 in these patients. Moreover, no information is available regarding the functionality of anti-SSX2 antibody responses and a possible impact on the course of the disease. Screening 1098 peripheral blood samples and 200 bone marrow samples of 194 MM patients, as well as 100 healthy donors serving as controls, we found six patients (3%) to present with SSX-2 specific antibodies. When we mapped the target epitopes using overlapping peptides for the whole SSX-2 sequence, we found the antibodies to be exclusively directed against amino acids 81–90. Remarkably, all antibodies were of the IgG3 subtype. In addition, SSX-2 antibodies were strictly antigen-specific and represented potent activators of the complement system. Correlating the antibody responses with clinical events, we found that the majority (5 out of 6) of seropositive patients had been antibody-negative before allogeneic stem cell transplantation (alloSCT) and had only developed anti-SSX2 antibodies after transplantation. Donor-derived antibody responses increased with depth of remission and, in case of recurrence of the disease, dropped to low or undetectable levels. Our data suggest that alloSCT is able to induce immune responses against myeloma specific SSX-2 antigen which is of low immunogenicity under normal conditions. Such antibody responses are of an effective phenotype and seem to correlate with protection from disease recurrence. To further characterize the biological role of transplantation-induced anti-SSX2 immune responses, we will analyze our patients for the presence of SSX-2-specific T cells which might be induced together with serological responses in the framework of an integrated immune response. Active immunotherapy might contribute to amplifying and shaping anti-SSX2 immune responses in myeloma patients, particularly after alloSCT. Disclosures: No relevant conflicts of interest to declare.

Analysis of Spontaneous Vs. Vaccine-Induced Antibody Responses Against Cancer-Testis Antigen MAGE-A3 in Cancer Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5087-5087
Author(s):  
Yanran Cao ◽  
Sacha Gnjatic ◽  
Vincent G. Brichard ◽  
Tim Luetkens ◽  
Sebastian Kobold ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Specific Antibodies ◽  
Fine Specificity ◽  
Specific Memory ◽  
Cancer Testis

Abstract Abstract 5087 Background: Cancer-testis antigens (CTA) are attractive targets for cancer immunotherapy based on their tumor-restricted expression and immunogenicity. A number of CTA, including Melanoma-associated antigen 3 (MAGE-A3), are already under clinical investigation and CTA have been shown to induce strong T cell and humoral immunity in cancer patients receiving active immunotherapy. However, little is known about the fine specificity and the function of vaccine-induced humoral immune responses and it is unclear how they relate to spontaneous CTA-specific immune responses occurring in a minority of patients. Methods: We have performed a longitudinal analysis of spontaneously occurring antibody responses against the CT antigen MAGE-A3 in sera (N=1537), which were collected from patients with multiple myeloma (N=355) over a period of 6 years. Antibody titers were determined by ELISA technique and a B cell ELISPOT assay was applied to estimate the number of MAGEA3-specific memory B cells in peripheral blood of the patients. Fine specificity of the antibody responses was examined using overlapping 20mer peptides spanning the whole sequence of MAGE-A3. The given IgG subtype was determined, and the quality of MAGE-A3-specific antibodies was analyzed using western blot as well as affinity assays. Results were compared to those obtained with MAGE-A3-specific antibody responses induced by vaccination with full-length MAGE-A3 protein and adjuvants AS02B or AS15 in patients with non-small cell lung cancer (NSCLC; N=15). Results: Out of 355 myeloma patients 4 (1.1%) evidenced spontaneous antibody responses against MAGE-A3 at least at one point during the course of their disease. Spontaneously occurring anti-MAGE-A3 humoral responses were usually of low titer. In contrast, all of the vaccinated patients showed high-titered and persisting antibody responses which usually appeared around week 6 after the first application of the vaccine. Accordingly, we found high frequencies of vaccine-induced MAGE-A3-specific memory B cells in the peripheral blood of NSCLC patients while they remained undetectable in most myeloma patients. Vaccine-induced antibody responses underwent affinity maturation reaching affinity levels of spontaneous immune responses after repeated cycles of treatment. MAGE-A3-specific antibodies consisted of IgG1 and IgG3>IgG2>IgG4 subtypes in vaccinated patients whereas spontaneously occurring antibodies were mainly of the IgG2 subtype. Spontaneous as well as vaccine-induced IgG antibodies both recognized the natural full-length protein. Analysis of the fine specificity of the antibody responses revealed that vaccine-induced antibodies recognized a much larger number of MAGE-A3 epitopes than spontaneously occurring antibodies. However, both, spontaneous as well as vaccine-induced responses, most frequently and strongly recognized a specific region within the MAGE-A3 protein corresponding to amino acids 51–70. Conclusions This study demonstrates for the first time important qualitative differences between spontaneously occurring and vaccine-induced antibody responses against the MAGE-A3 antigen in cancer patients. While the potential of both types of antibody responses to promote antigen uptake and induction of T cell responses by antigen-presenting cells might differ, they both recognized the same restricted region within the MAGE-A3 protein. The latter finding might be of importance for the design of future immunotherapies targeting MAGE-A3. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antibody responses to rhesus cytomegalovirus glycoprotein B in naturally infected rhesus macaques

2003 ◽  
Vol 84 (12) ◽  
pp. 3371-3379 ◽  
Author(s):  
Yujuan Yue ◽  
Shan Shan Zhou ◽  
Peter A. Barry
Keyword(s):  
Specific Antibody ◽  
Transmembrane Domain ◽  
Solid Phase ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Full Length ◽  
Glycoprotein B ◽  
Primate Model ◽  
Specific Antibodies ◽  
Rhesus Cytomegalovirus

Rhesus cytomegalovirus (RhCMV) exhibits strong parallels with human CMV (HCMV) in terms of nucleic and amino acid identities, natural history, and mechanisms of persistence and pathogenesis in its natural host, rhesus macaques (Macaca mulatta). To determine whether this non-human primate model would be useful to assess vaccine strategies for HCMV, host immune responses to RhCMV glycoprotein B (gB) were evaluated in RhCMV-infected monkeys. Total protein extracts were prepared from cells transiently transfected with an expression plasmid for either the full-length gB or a derivative (gBΔ, 1–680 aa) lacking both the transmembrane domain and cytoplasmic tail. Western blot analysis showed identical reactivity of macaque sera with full-length gB and its derivative gBΔ, indicating that the immunodominant epitopes of gB are contained in the extracellular portion of the protein. Using gBΔ extract as a solid phase, a sensitive and specific ELISA was established to characterize gB antibody responses in monkeys acutely and chronically infected with RhCMV. During primary infection (seroconversion), gB-specific antibodies developed concurrently and in parallel with total RhCMV-specific antibodies. However, during chronic infection gB-specific antibody responses were variable. A strong correlation was observed between neutralizing and gB-specific antibody levels in RhCMV-seropositive monkeys. Taken together, the results of this study indicate that, similar to host humoral responses to HCMV gB, anti-gB antibodies are an integral part of humoral immunity to RhCMV infection and probably play an important protective role in limiting the extent of RhCMV infection. Thus, the rhesus macaque model of HCMV infection is relevant for testing gB-based immune therapies.

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