Antibody-dependent Cellular Cytotoxicity Titers Research Articles

SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines.

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.

Potential of Antibody-Dependent Cellular Cytotoxicity in Acute and Recovery Phases of SARS-CoV-2 Infection

Abstract Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic that has resulted in millions of casualties. Although researchers have reported the existence of neutralizing antibodies and viral T cell immunity against SARS-CoV-2, little is known about the presence of antibody-dependent cellular cytotoxicity (ADCC) and its role in combating SARS-CoV-2 infection. Methods: Nineteen acute COVID-19 patients at the First Affiliated Hospital of Guangzhou Medical University from January to February, 2020 and 55 recovery COVID-19 patients at the Second Peoples Hospital of Changde City from February, 2020 to February, 2021 were recruited in this study. Longitudinal plasma samples were collected. A virus-specific ADCC assay was performed to study the COVID-19 plasma samples. The correlations between ADCC and total IgG titer, including anti-RBD, anti-N, and neutralizing antibody titer were analyzed. Results: A high level of ADCC with 0.86% of IFN-γ+CD107a+ NK cells induced by anti RBD antibodies and with 0.54% of IFN-γ+CD107a+ NK cells induced by anti N antibodies was observed. This activity peaked at 3 weeks after disease onset with 1.16% and 0.63% of IFN-γ+CD107a+ NK cells induced by anti RBD and anti N antibodies respectively, declined to 0.32% and 0.32% of IFN-γ+CD107a+ NK cells respectively after more than 2 months, and persisted for 12 months after disease onset. The ADCC did not aggravate the severity of COVID-19 in terms of sequential organ failure assessment, although ADCC decreased with the age of COVID-19 patients. Interestingly, ADCC response is not correlated with neutralizing antibody titer or total IgG titers against S protein RBD and N protein in acute patients. ADCC in recovered patients showed a significant correlation with anti RBD IgG titer (R 2 = 0.33, P < 0.001). Conclusion: Antibodies from COVID-19 patients against the N protein and S protein RBD domains could stimulate high levels of ADCC response. Our results provide evidence that vaccination should not only focus on neutralizing antibodies but also binding antibodies that may facilitate the antiviral function of ADCC, especially in the elderly.

High Antibody-Dependent Cellular Cytotoxicity Responses Are Correlated with Strong CD8 T Cell Viral Suppressive Activity but Not with B57 Status in HIV-1 Elite Controllers

The role of Antibody-dependent cellular cytotoxicity (ADCC) responses in HIV-1 controllers is still unclear due to the heterogeneity of these patients. We analyzed 67 HIV-1 controllers and found significantly higher levels of ADCC antibodies in controllers versus viremic subjects (p = 0.017). Moreover, multivariate analysis revealed significantly higher ADCC titers in HLA B57- controllers compared to HLA-B57+ ones (p = 0.0086). These data suggest a role for ADCC in immune control of HIV, especially in HLA B57 negative controllers.

Age-Associated Cross-reactive Antibody-Dependent Cellular Cytotoxicity Toward 2009 Pandemic Influenza A Virus Subtype H1N1

During the 2009 pandemic of influenza A virus subtype H1N1 (A[H1N1]pdm09) infection, older individuals were partially protected from severe disease. It is not known whether preexisting antibodies with effector functions such as antibody-dependent cellular cytotoxicity (ADCC) contributed to the immunity observed. We tested serum specimens obtained from 182 individuals aged 1-72 years that were collected either immediately before or after the A(H1N1)pdm09 pandemic for ADCC antibodies to the A(H1N1)pdm09 hemagglutinin (HA) protein. A(H1N1)pdm09 HA-specific ADCC antibodies were detected in almost all individuals aged >45 years (28/31 subjects) before the 2009 A(H1N1) pandemic. Conversely, only approximately half of the individuals aged 1-14 years (11/31) and 15-45 years (17/31) had cross-reactive ADCC antibodies before the 2009 A(H1N1) pandemic. The A(H1N1)pdm09-specific ADCC antibodies were able to efficiently mediate the killing of influenza virus-infected respiratory epithelial cells. Further, subjects >45 years of age had higher ADCC titers to a range of seasonal H1N1 HA proteins, including from the 1918 virus, compared with younger individuals. ADCC antibodies may have contributed to the protection exhibited in older individuals during the 2009 A(H1N1) pandemic. This work has significant implications for improved vaccination strategies for future influenza pandemics.

Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV mac251 Challenge

We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed by envelope protein boosting, elicits broad cellular immunity and functional, envelope-specific serum and mucosal antibodies that correlate with protection from high-dose SIV and simian/human immunodeficiency virus (SHIV) challenges in rhesus macaques. Here we extended these studies to compare the standard i.n./i.t. regimen with additional mucosal administration routes, including sublingual, rectal, and vaginal routes. Similar systemic cellular and humoral immunity was elicited by all immunization routes. Central and effector memory T cell responses were also elicited by the four immunization routes in bronchoalveolar lavage fluid and jejunal, rectal, and vaginal tissue samples. Cellular responses in vaginal tissue were more compartmentalized, being induced primarily by intravaginal administration. In contrast, all immunization routes elicited secretory IgA (sIgA) responses at multiple mucosal sites. Following a repeated low-dose intrarectal (i.r.) challenge with SIV(mac251) at a dose transmitting one or two variants, protection against acquisition was not achieved except in one macaque in the i.r. immunized group. All immunized macaques exhibited reduced peak viremia compared to that of controls, correlated inversely with prechallenge serum antienvelope avidity, antibody-dependent cellular cytotoxicity (ADCC) titers, and percent antibody-dependent cell-mediated viral inhibition. Both antibody avidity and ADCC titers were correlated with the number of exposures required for infection. Notably, we show for the first time a significant correlation of vaccine-induced sIgA titers in rectal secretions with delayed acquisition. Further investigation of the characteristics and properties of the sIgA should elucidate the mechanism leading to this protective effect.

Delayed generation of antibodies mediating human immunodeficiency virus type 1-specific antibody-dependent cellular cytotoxicity in vertically infected infants. WITS Study Group. Women and Infants Transmission Study.

Human immunodeficiency virus type 1 (HIV-1)-specific antibody-dependent cellular cytotoxicity (ADCC) antibody titers were serially measured from birth to 24 months in the plasma of 14 intrapartum-infected and 10 uninfected infants born to HIV-1-infected women. The mean ADCC antibody titers measured at birth in infected and uninfected infants were similar (10(-3.9) and 10(-4.0), respectively), suggesting that ADCC antibodies did not protect infants from the intrapartum transmission of HIV-1. In infected infants, ADCC titers at birth did not predict subsequent clinical disease course. The active production of HIV-1-specific ADCC antibodies was detected in most infected infants only after 12 months of age, well after the loss of passively acquired maternal ADCC antibody. The delayed production of ADCC antibodies in infancy may account, in part, for the less efficient control of viral replication and more rapid disease progression following vertical infection compared with that in adults.

Identification of cross-reactive antigenic target regions for HIV type 1-specific antibody-dependent cellular cytotoxicity.

Monkey-derived hyperimmune antisera against 40 peptides, together representing the entire envelope gp120 of HIV-1LAI, were used to map antibody-dependent cellular cytotoxicity (ADCC) target regions. Four regions corresponding to amino acids 65-126, 152-230, 248-330, and 445-466 were found to contain epitopes inducing ADCC activity not only against HIV-1LAI-infected cells but also against cells infected with HIV-1SF2 and clinical isolates of HIV-1. When comparing seroreactivity to the individual peptides with ADCC titers none of the regions seemed to be dominant. These results thus describe cross-reactive regions involved in the functional immunity against HIV-1 gp120.

Positive Correlation Between the Natural Killer and gp 120/41-Specific Antibody-Dependent Cellular Cytotoxic Effector Functions in HIV-Infected Individuals

Using our recently developed target system model of env gene-transfected cells for gp120/41-specific antibody-dependent cellular cytotoxicity (ADCC) assays, we evaluated the ADCC effector function of the peripheral blood mononuclear cells (PBMC) in 39 human immunodeficiency virus type 1 (HIV-1)-infected individuals. The natural killer (NK) activity of the PBMC from these individuals against K562 was also determined. A significant positive correlation (p < or = 0.05, r = 0.37) was found between these two activities. On the basis of our data, we built a regression equation for the two activities whereby the ADCC effector function of PBMC of an HIV-infected individual can be predicted from their NK activity. We also found that the endpoint titer of a given serum for ADCC-mediating antibodies in the ADCC assay varied depending on the NK activity of the effector cells used: The effectors with high NK activity tended to give higher titers as compared with the effectors with low NK activity. To our knowledge, this is the first formal documentation of the existence of a positive correlation between the ADCC and NK activities of the PBMC. It also shows that the ADCC titer of serum in ADCC assay may vary depending on the NK activity of the effector cells used. This observation underscores an important variable of ADCC assays. Using our statistical model, one can predict the ADCC effector function of the PBMC from HIV-infected individuals from their NK activity and thus help clarify the role of this important immune response in HIV infection and AIDS prognosis.

Association between Anti-Human Immunodeficiency Virus Type 1 (HIV-I) Antibody-Dependent Cellular Cytotoxicity Antibody Titers at Birth and Vertical Transmission of HIV-I

Because vertical transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant occurs in only 15%-35% of possible opportunities, natural immune defenses of the mother, fetus, or neonate may be protective against infection. The relation between antibody-dependent cellular cytotoxicity (ADCC) antibodies and HIV-1 infection was explored in 78 neonates born to HIV-infected women. More than 90% of sera had measurable ADCC titers against HIV-1IIIB. Infant titers were closely correlated with maternal titers but were independent of total IgG and total antibody reactive to the same strain in whole virus ELISA. At birth, mean ADCC antibody levels of infants or their mothers were the same for infants who were infected and those who ultimately seroreverted and remained healthy. ADCC antibody titers against HIV-1SF2 were weakly correlated with anti-HIV-1IIIB titers and did not predict protection from HIV-1 infection. High levels of anti-HIV-1 ADCC antibody at birth are not protective against vertical transmission of HIV-1.

Comparison of Measles Virus-Specific Antibodies with Antibody-Dependent Cellular Cytotoxicity and Neutralizing Functions

Measles virus-specific antibodies with antibody-dependent cellular cytotoxicity (ADCC) and neutralizing functions were compared in 25 healthy women. ADCC antibody was measured in a 12-h 51Cr release assay using peripheral blood mononuclear cells as effectors and Raji cells persistently infected with measles as targets. Neutralizing antibody was determined by the plaque neutralization test (PNT). ADCC and PNT titers correlated well (r = .80, P < .001). ADCC titers ranged from < 10 to > 10(6) and averaged 1.3 logs higher than PNT titers. Three sera with PNT titers of < 120, including 1 with a titer of < 8 (< 10(0.9)), had ADCC titers of > or = 10(2.5). Among subjects born in the United States, ADCC titers, but not PNT titers, correlated inversely with the year of birth, suggesting that ADCC antibody may be more indicative than neutralizing antibody of differences between naturally and vaccine-acquired immunity. These data suggest a possible role for ADCC in protection or recovery from measles.

Antibody-dependent cellular cytotoxicity against HIV-1 in sera of immunized chimpanzees

After immunization of chimpanzees against HIV antigens, antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) were evaluated and compared with anti-HIV-antibody levels detected by enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers. Adult chimpanzees were immunized with different HIV-1 (LAV-BRU) antigen preparations: recombinant vaccinia virus (rVV) expressing gp160, p25 or p27nef; formalin- and beta-propiolactone-inactivated whole virus (inHIV); soluble recombinant gp160 either associated or not associated with other HIV proteins; a 25-mer peptide from the V3 region of gp120 coupled with KLH (V3-KLH). Immunization with the various rVV mixtures induced no or borderline ADCC increase above preimmune serum levels. Stronger and more sustained reactivity was elicited by inHIV. Purified HIV antigens elicited ADCC activity when the chimpanzees were naive; ADCC increased or remained at the same level when the animals had been preimmunized with rVV and/or inHIV. This type of reactivity apparently did not depend on whether gp160 alone or mixed with other proteins was used for immunization. The injection of V3-KLH resulted in only little, if any, recall ADCC response. ELISA antibody titers significantly correlated with ADCC and neutralizing antibody titers, but serum ADCC was independent of neutralizing antibody titers, an indication that the two latter serum activities are mediated by independent antibodies. Therefore, ADCC is elicited in the same manner as other antibody activities by the immunization of chimpanzees with inHIV or with purified recombinant HIV antigen preparations. The results obtained from the three chimpanzees of this series, which were subsequently challenged with infectious virus through the intravenous route, suggest that serum ADCC may be considered for vaccination purposes.

Biological significance of the antibody response to HIV antigens expressed on the cell surface.

Human antibodies to HIV antigens expressed on the surface of infected cells may inhibit cell fusion with uninfected CD 4-positive cells and mediate killing of the infected cells by effector cells bearing the Fc receptor. Sequential sera from ten HIV-antibody seroconverted men, of which five progressed to ARC or AIDS (CDC stage IV) during the follow-up period of two years, were tested for the ability to inhibit CD 4-dependent cell fusion, (CFI) and to mediate antibody-dependent cellular cytotoxicity (ADCC). Nine patients developed HIV-specific ADCC and seven CFI-antibodies using the HIV strain HTLV-IIIB as target antigen. These antibodies appeared approximately at the same time 2-12 months after primary infection, defined as antibody seroconversion or antigenaemia. ADCC antibodies were detectable at higher titers as compared to CFI-antibodies. All sera of asymptomatic individuals (CDC stage II and III) were CFI antibody positive and had a higher mean ADCC titer as compared to sera from patients progressing to AIDS or ARC. ADCC and CFI antibodies coincided in some cases in the complete absence of core antibodies. Because the relationship between ADCC and CFI was not exclusive it is concluded that distinct domains of the HIV envelope induce natural antibodies mediating ADCC and CFI.

Antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus. Presence at different clinical stages.

The presence of antibodies mediating antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV)-infected target cells was investigated with 170 sera from patients with varying severity of HIV infection. Approximately 40% of sera from individuals representing all stages of infection were ADCC-positive when tested against HTLV-IIIB infected 0937 clone 2 target cells. The positive sera had higher HIV antibody titers as measured by enzyme-linked immunosorbent assay compared with ADCC-negative sera. ADCC titers were lower in patients with acquired immune deficiency syndrome than in asymptomatic carriers. This decline in ADCC titer was not correlated with a general decrease of HIV antibodies. No correlation between the CD4:CD8 lymphocyte ratio and ADCC activity was found. The possible beneficial effect of ADCC-inducing antibodies early in infection is discussed in relation to the effect of ADCC-inducing antibodies in other retrovirus systems and to the nature of lentivirus infections.

Antibody-dependent cellular cytotoxicity. Relation to stage and disease course in North American patients with nasopharyngeal carcinoma.

A prospective study of North American patients, mostly white, with different histopathologic types of nasopharyngeal carcinoma was initiated approximately five years ago. Several anti-Epstein-Barr virus (EBV) serologic tests are being evaluated; one is the antibody-dependent cellular cytotoxicity (ADCC) assay, which measures antibodies to an EBV-induced membrane antigen component. A low ADCC titer at diagnosis reflects a poor prognosis, and the determination of antibody titers by this assay identifies patients in whom recurrent disease is likely to develop after conventional radiation therapy for World Health Organization types 2 and 3 carcinomas. Of the patients who had high ADCC titers at diagnosis, 80% survived three years or longer, whereas 50% of the patients with low titers survived three years, and only 35% survived five years. High and low ADCC titers were seen in all stages (except in Ho stage V), and the distribution of patients by high and low ADCC titers was similar in each of the stage groupings. We conclude that the ADCC titer at the time of diagnosis is generally predictive of the prognosis. Clinical staging is the traditional approach for predicting prognosis, but determination of the ADCC titer can be used to segregate patients within the stage groups into those with "good" and "poor" prognoses. Serologic testing may eventually become one of the methods for staging patients with WHO types 2 and 3 nasopharyngeal carcinoma.

Antibody-dependent cellular cytotoxicity and disease course in North American patients with nasopharyngeal carcinoma: a prospective study.

It has previously been reported that antibody-dependent cellular cytotoxicity (ADCC) levels determined at diagnosis against Epstein-Barr virus (EBV)-specific membrane antigens (MA) are predictive of disease course following therapy in patients with nasopharyngeal carcinoma (NPC). In general, survival was significantly shorter following therapy in patients with low ADCC titers at diagnosis versus those with high titers. To examine this further, a prospective study on North Americans with different histopathological types of this disease was initiated approximately 5 years ago. The results to date tend to support the conclusions drawn from the retrospective study for patients with the more poorly differentiated types (WHO 2 and WHO 3) of this disease. Over the first 3 years of this study, approximately 75% of the patients in the "high" category have remained clinically disease-free for 3 years or longer as opposed to approximately 35% of the patients in the "low" group. Disease progression rates were calculated to be approximately four times higher in the low group. Similar trends were noted in actual survival rates over a 3-year period. ADCC titers were in general found to be relatively stable in sequential serum samples from the same patient, with some exceptions. With the exceptions, however, changes in ADCC titers also reflected disease course. These results indicate, therefore, that anti-EBV ADCC titers are predictive of disease course in patients with the poorly differentiated types of NPC.

IgA antibody, antibody-dependent cellular cytotoxicity and prognosis in patients with nasopharyngeal carcinoma.

Immunoglobulin fractions containing antibodies to the Epstein-Barr virus (EBV) were isolated from different sera and tested in the antibody-dependent cellular cytotoxicity (ADCC) assay. All cytotoxic activity resided in the IgG fraction. IgA antibodies were not cytotoxic in this assay against cells expressing the EBV-induced membrane antigen complex. However, IgA antibodies were able to block the IgG-mediated ADCC reaction, indicating that the IgA and IgG antibodies recognized the same EVB-specific antigenic determinants. This was supported by results from radioimmune precipitation experiments. Our findings suggest that low ADCC titers previously identified in the sera of patients with nasopharyngeal carcinoma (NPC) who had a poor prognosis could be due to the blocking activity of IgA antibodies. The results further suggest that IgA antibodies are detrimental to the patient with this disease, if one assumes that ADCC functions in vivo in immunity to this tumor

Immune Response to Inactivated Syngeneic Mammary Adenocarcinoma Cells. II. Parameters of Immunogenicity in DBA/2 Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;

With the use of the DBA/2 mammary adenocarcinoma (T1699), the early events that occurred after a single sc injection of untreated or inactivated tumor cells in the syngeneic host were investigated. Examination of the vascularization of the site of sensitization revealed that by day 3, injection of irradiated T1699 tumor cells (XR-T1699) induced the same high level of blood vessel formation as did untreated T1699 tumor cells (T1699u). Whereas the former then decreased, the latter peaked at day 5 and gradually tapered off. Inoculation sites of mitomycin C-treated T1699 tumor cells (T1699m) were poorly vascularized at all times and stimulated a predominantly granulocyte host cell response that peaked at day 1. XR-T1699 caused a peak granulomatous response at day 5, which was distinguished by increased levels of mononuclear cell infiltration. XR-T1699 showed much longer survival and replicating potential than did T1699m in vivo. However, an increased dose of radiation to 30 krads did not significantly reduce the ability of the XR-T1699 immunization to induce anti-T1699 antibody synthesis and protection against subsequent tumor cell challenge. Surgical excision of the XR-T1699 granuloma at day 3 prevented immunization as indicated by the lack of significant antibody-dependent cellular cytotoxicity (ADCC) activity in the sera of these mice and by their inability to reject a subsequent challenge with T1699u However, removal at day 5 did not decrease the ADCC titer below levels seen in XR-T1699-sensitized mice that were not surgically treated and did not alter the ability of those mice to reject a T1699u challenge.

Epstein-Barr virus-specific antibody-dependent cellular cytotoxicity in patients with Burkitt's lymphoma.

Coded sera from 54 patients with African Burkitt's lymphoma (BL) were titrated for antibodies against an Epstein-Barr virus (EBV)-induced membrane antigen in the antibody-dependent cellular cytotoxicity (ADCC) assay. The titers were then correlated with the progression of lymphoma growth following chemotherapy. In 74% of the patients with high ADCC titers (greater than 3,840), lymphomas showed partial or complete regression following therapy. In the medium-titered group (240-3,840), 36% of the lymphomas showed some response to therapy, while only 29% of the lymphomas in the low group (less than 240) responded to treatment. These preliminary results indicated that, as previously reported for patients with nasopharyngeal carcinoma, ADCC titers may be a prognotic value in patients with this EBV-associated disease. In an attempt to determine the identity of the ADCC antigen, some of these sera were examined for antibody to the four major MA components so far identified in the membrane of EBV-infected Raji cells. Sera with high ADCC titers in general contained antibody to the four major MA components, while low-titered sera usually contained antibody to three or less of these proteins. There were exceptions to this pattern, however, indicating that the ADCC antigen might differ from the four EBV-induced membrane components so far identified.

Antibody‐dependent cellular cytotoxicity against epstein‐barr virus‐associated antigens in african patients with nasopharyngeal carcinoma

Antibody-dependent cellular cytotoxicity (ADCC) was performed on serum samples from African patients with nasopharyngeal carcinoma (NPC) to determine whether antibody titers determined by this assay might be of prognostic value in this disease. The serum donors were divided into two groups: (1) those individuals who died within 2 years following diagnosis of NPC; and (2) individuals who responded well to therapy and surivived for more than 2 years following diagnosis. The ADCC GMT for the survivor group was significantly higher than the GMT for non-survivors (%5,410 versus 615). Interestingly, there were a number of discordant sera in the non-survivor group that had very low ADCC titers (less than 240) at diagnosis in the presence of high VCA titers. When ADCC titers were compared with anti-EA or IgA antibody titers to VCA, a statistically significant inverse correlation was noted. These data suggest that ADCC titers might be of prognostic importance in African NPC.