David Venzon

Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals.

Infection with HIV results in an incremental loss of T helper cell (TH) function, which can occur years before CD4 cell numbers are critically reduced and AIDS is diagnosed. All TH function is not affected, however, because B cell activation and hypergammaglobulinema are also characteristic of this period. Recently, in a murine model of AIDS an early loss in production of the CD4 cytokines IL-2 and IFN-gamma was correlated with an increase in the B cell stimulatory cytokines IL-4, IL-5, and IL-10. We therefore assessed the production of IL-4 generated by PBL from HIV-seropositive (HIV+) individuals who did not have AIDS, yet who exhibited different TH functional categories based on their IL-2 production profiles. We observed that the decreases in recall antigen-stimulated IL-2 production were accompanied by an increase in IL-4 production. The loss of recall antigen-stimulated responses in HIV+ individuals could be reversed in vitro by anti-IL-4 antibody. Our results suggest that the TH functions assessed by IL-4 production replace the normally dominant TH function of antigen-stimulated IL-2 production in the progression toward AIDS, and raise the possibility of cytokine cross-regulation in AIDS therapy.

Surgery to cure the Zollinger-Ellison syndrome.

BACKGROUND AND METHODS The role of surgery in patients with the Zollinger-Ellison syndrome is controversial. To determine the efficacy of surgery in patients with this syndrome, we followed 151 consecutive patients who underwent laparotomy between 1981 and 1998. Of these patients, 123 had sporadic gastrinomas and 28 had multiple endocrine neoplasia type 1 with an imaged tumor of at least 3 cm in diameter. Tumor-localization studies and functional localization studies were performed routinely. All patients underwent surgery according to a similar operative protocol, and all patients who had surgery after 1986 underwent duodenotomy. RESULTS The 151 patients underwent 180 exploratory operations. The mean (+/-SD) follow-up after the first operation was 8+/-4 years. Gastrinomas were found in 141 of the patients (93 percent), including all of the last 81 patients to undergo surgery. The tumors were located in the duodenum in 74 patients (49 percent) and in the pancreas in 36 patients (24 percent); however, primary tumors were found in lymph nodes in 17 patients (11 percent) and in another location in 13 patients (9 percent). The primary location was unknown in 24 patients (16 percent). Among the patients with sporadic gastrinomas, 34 percent were free of disease at 10 years, as compared with none of the patients with multiple endocrine neoplasia type 1. The overall 10-year survival rate was 94 percent. CONCLUSIONS All patients with the Zollinger-Ellison syndrome who do not have multiple endocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure.

Determinants of metastatic rate and survival in patients with zollinger-ellison syndrome: A prospective long-term study

BACKGROUND/AIMS It is unclear whether tumor location, size, or the presence of multiple endocrine neoplasia type 1 (MEN-1) alters metastatic rate and survival in patients with pancreatic endocrine tumors. The purpose of this study was to determine the prognostic factors of survival and metastatic rate in patients with Zollinger-Ellison syndrome (ZES). METHODS Data were analyzed from 185 consecutive patients with ZES who were followed up prospectively. RESULTS Liver metastases were present in 24% of patients and correlated with the size of the primary tumor. Duodenal tumors were smaller than pancreatic tumors. Liver metastases occurred more often (P < 0.00001) with pancreatic than duodenal tumors, whereas the metastatic rate to lymph nodes was not different. Survival of patients with liver but not lymph node metastases was shortened. In patients with sporadic ZES, liver metastases were more common during the initial evaluation and survival was decreased compared with patients with MEN-1; however, during follow-up, an equal percentage of patients with and without MEN-1 developed liver metastases. CONCLUSIONS Survival was primarily determined by the presence of liver metastases. The frequency of liver metastases depends on the size and location of the primary tumor and on the presence of MEN-1 at the initial presentation. Metastases to the lymph nodes do not depend on these factors. A benign and malignant form of ZES exists.

Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen.

PURPOSE We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups. PATIENTS AND METHODS Seventy-two patients (39 adults and 33 children) were treated with protocol 77-04 between 1977 and 1985. All patients, except those with resected abdominal disease, received 15 cycles of a combination of cyclophosphamide (CTX), doxorubicin (ADR), prednisone (PRED), vincristine (VCR), high-dose methotrexate (MTX), and intrathecal (IT) therapy. Forty-one patients (20 adults and 21 children) were treated with protocol 89-C-41, which has been used since 1989. High-risk patients received four alternating cycles (with a total duration of 12 to 15 weeks) of an intensified version of protocol 77-04 without PRED (CODOX-M), and a new drug combination consisting of ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC). Low-risk patients received three cycles of the CODOX-M regimen. High-risk patients were randomized to either receive or not receive granulocyte-macrophage colony-stimulating factor (GM-CSF). RESULTS Event-free survival (EFS) in protocol 77-04 was 56% at 2 years and beyond. EFS in protocol 89-C-41 was 92% at 2 years and beyond. GM-CSF was associated with increased thrombocytopenia. CONCLUSION Adults and children with SNCL have a similar prognosis when treated with the same chemotherapy. EFS in high-risk patients has been markedly improved by including IVAC in protocol 89-C-41, and excellent results can be achieved with only four cycles of therapy. In protocol 89-C-41, GM-CSF was not beneficial.

Somatostatin Receptor Scintigraphy: Its Sensitivity Compared with That of Other Imaging Methods in Detecting Primary and Metastatic Gastrinomas: A Prospective Study

Studies have shown that many tumors, such as gastroenteropancreatic tumors (pancreatic endocrine tumors, carcinoid tumors), various lymphomas, and central nervous system tumors (meningiomas, astrocytomas), have a high density of somatostatin receptors and can be imaged in vivo by using somatostatin receptor scintigraphy with either [123I-Tyr3]octreotide or [111In-DTPA-DPhe1]octreotide [1-6]. Recently, [111In-DTPA-DPhe1]octreotide was approved for use in the United States for the imaging of primary and metastatic neuroendocrine tumors [6]. Many conventional imaging methods, including ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), selective arteriography, and selective intra-arterial secretin stimulation with venous sampling, already exist for the localization of gastroenteropancreatic tumors [7-10]. Although numerous studies have shown somatostatin receptor scintigraphy to be sensitive for the detection of neuroendocrine tumors, information on its sensitivity compared with that of other imaging techniques is limited; thus, it is difficult for the practitioner to define the potential role of somatostatin receptor scintigraphy in the evaluation of a patient with a gastroenteropancreatic syndrome. This is important because somatostatin receptor scintigraphy and the other imaging studies are expensive [1] and because accurate localization of the primary tumor is particularly important for the management of neuroendocrine tumors, which are often small and difficult to find [11-13]. Furthermore, accurate assessment of the extent of the tumor is essential for making decisions about resectability, tumoricidal therapy, disease progression, and liver transplantation [8, 14, 15]. Because neuroendocrine tumors are uncommon [8], many studies do not provide the data needed to define the role of somatostatin receptor scintigraphy in the management of these tumors. Several studies have compared the sensitivity of somatostatin receptor scintigraphy with that of ultrasonography or CT by assessing tumor detection on a lesion-by-lesion basis. However, few studies have compared somatostatin receptor scintigraphy with the most sensitive conventional imaging studies, particularly selective arteriography and MRI using STIR (short-time inversion-inversion recovery sequences) [8, 16, 17]. Thus, it is difficult to know the sensitivity and the role of somatostatin receptor scintigraphy in relation to these methods. Furthermore, only one study [18] has evaluated the possibility of conventional imaging combined with somatostatin receptor scintigraphy; therefore, it remains unclear whether additional localization studies are helpful when somatostatin receptor scintigraphy results are negative. Finally, most studies have not assessed the sensitivity of somatostatin receptor scintigraphy relative to other methods in different clinical situations. Patients with gastroenteropancreatic tumors are assessed for location of the primary tumor (to assist in possible tumor resection [7, 11-13]), for metastasis to the liver (for possible resectability [8, 14, 19, 20]), for the need for tumoricidal therapy [21], and for distant metastases (for possible specific tumoricidal therapies, such as local radiation to bone metastases [22]). Different localization methods are better for certain clinical situations [8, 9, 17], and somatostatin receptor scintigraphy needs to be compared with other methods in each of these clinical circumstances. Sixty percent to 90% of patients with the Zollinger-Ellison syndrome have malignant tumors, and their tumors thus resemble all pancreatic endocrine tumors with the exception of insulinomas [8, 23, 24]. The Zollinger-Ellison syndrome occurs more frequently than other malignant pancreatic endocrine tumors. Therefore, several groups, including ours, have a sufficient number of patients with this syndrome to be able to systematically address questions about localization in different clinical situations [8, 25, 26]. Gastrinomas resemble other, less common pancreatic endocrine tumors in that they are composed of amine precursor uptake and decarboxylation (APUD) cells and have similar growth patterns, locations, imaging properties, metastatic rates, immunohistochemistry, and rates of occurrence of somatostatin receptors [24, 27]. Gastrinomas are therefore an excellent model from which to obtain information that is also pertinent to the less common pancreatic endocrine tumors [25]. We prospectively compared the ability of somatostatin receptor scintigraphy with that of other conventional localization methodsultrasonography, CT, MRI, bone scanning, and selective angiographyin the localization of primary and metastatic gastrinoma in patients with the Zollinger-Ellison syndrome. Methods We prospectively studied 80 consecutive patients with the Zollinger-Ellison syndrome who were admitted to the National Institutes of Health (NIH) between June 1994 and May 1995. Our study is part of a prospective study of patients with the Zollinger-Ellison syndrome that has been ongoing at the NIH since 1974, as approved by the clinical research committee of the National Institute of Diabetes and Digestive and Kidney Diseases. Thirty-one of the patients had no previous gastrinoma resection, and 49 had had noncurative resections of gastrinomas 0.25 years to 13 years before the study. The Zollinger-Ellison syndrome was diagnosed as described elsewhere [28]. Serum gastrin levels were determined by Bioscience Laboratories (New York, New York). The diagnostic criteria for the presence of multiple endocrine neoplasia type I in a patient with the Zollinger-Ellison syndrome have been described elsewhere [29]. Basal acid output and maximal acid output were determined for each patient by using methods described previously [30]. Doses of oral antisecretory drug were determined by establishing the dose required to reduce gastric acid output to less than 10 mEq per hour before the next dose of medication and to less than 5 mEq per hour for patients who had had gastric acid-reducing surgery or who had advanced esophageal disease [31]. Specific Protocol The localization and the extent of gastrinomas were evaluated in all patients as described elsewhere [17, 32] by using upper gastrointestinal endoscopy, CT, MRI, transabdominal ultrasonography [33], and bone scanning. With MRI, T1-weighted spin-echo sequences and STIR sequences were obtained with a repetition time of 400 to 600 ms and an echo time of 10 ms as described [16]. We did CT as described [16, 17] at 10-mm thickness with an oral contrast agent (diatrizoate sodium, Winthrop-Breon, Rensselaer, New York) with and without the rapid (2 mL/s) intravenous injection of the contrast agent iopamidol 300 (Winthrop-Breon). If surgical exploration was being considered or the extent of disease remained unclear, selective abdominal angiography was done with injection of the splenic, superior mesenteric, gastroduodenal, and hepatic arteries as described elsewhere [17, 34]. One radiologist evaluated the results of all conventional imaging studies. For somatostatin receptor scintigraphy studies, patients were hydrated before and after the intravenous injection of [111In-DTPA-DPhe1]octreotide and were given a laxative on the night of administration to avoid artifacts from radioactive accumulation in the intestines. Each patient received 6 mCi of [111In-DTPA-DPhe1]octreotide intravenously as recommended by the manufacturer for single-photon emission computed tomographic (SPECT) imaging (Mallinckrodt Diagnostic Imaging Service Radiopharmacy, Beltsville, Maryland). Images were obtained 4 and 24 hours after injection using a TRIONIX (Twinburg, Ohio) or ADAC (Milipitas, California) dual-headed camera with 20% windows at 173 and 247 keV. At 4 hours, a 30-minute whole-body scan was obtained; 10-minute planer spot views of the abdomen and other regions were obtained as needed. At 35 minutes and at 24 hours, SPECT images of the abdomen were obtained. Forty-second, 128 128 matrix SPECT images were acquired at 4-degree intervals over 360 degrees. The images were reconstructed with the manufacturers software using a standard filter back projection algorithm. A Hamming filter was used. Images were displayed as orthogonal (transverse, coronal, sagittal) sections and as reprojected views. Results of somatostatin receptor scintigraphy were obtained while the investigator was blinded to the results of the conventional imaging studies. Surgical exploration was done in all new patients and all patients who had a positive extrahepatic gastrinoma localized, had no liver metastases, had multiple endocrine neoplasia type I or a recent exploration (< 2 years), and had had exploratory laparotomy for possible gastrinoma resection (n = 15). All patients with possible liver metastases had percutaneous CT- or ultrasonography-guided biopsies (n = 24). Statistical Analysis The Fisher exact test was used to compare independent percentages, and the McNemar test was used to compare sensitivities in the same patients. Two-tailed P values and 95% CIs from the StatXact statistical package (Version 3.0, Cytel Software Corp., Cambridge, Massachusetts) are reported. P values less than 0.05 were considered statistically significant. Results The clinical and laboratory characteristics of the 80 study patients are shown in Table 1. These patients resemble patients in other large series [8, 35] with regard to sex, age, multiple endocrine neoplasia type I, basal acid output, maximal acid output, fasting serum gastrin concentration, and disease duration. Table 1. Clinical and Laboratory Characteristics of Patients with the Zollinger-Ellison Syndrome* Somatostatin receptor scintigraphy detected tumors either inside or outside of the liver in 56 of the 80 patients (70%); conventional imaging studies were significantly less sensitive (P < 0.001) (Figure 1). Angiography, CT, and MRI each detected tumors in 38% to 45% of patients; ultrasonograph

Prospective Study of the Clinical Course, Prognostic Factors, Causes of Death, and Survival in Patients With Long-Standing Zollinger-Ellison Syndrome

PURPOSE The long-term clinical course of unselected patients with gastrinomas as well as other functional pancreatic endocrine tumors (PETs) in whom the excess-hormone state is controlled is largely unknown. To address this issue, patients with gastrinomas were assessed. PATIENTS AND METHODS Two hundred twelve patients with Zollinger-Ellison syndrome (ZES) were prospectively studied. All had controlled acid hypersecretion and were assessed yearly, with a mean follow-up period of 13.8+/-0.6 years (range, 0.1 to 31 years). Annual assessments of possible factors that might affect prognosis or treatment approaches were performed, such as those for tumor size and location; the presence, location, and extent of metastases; and the occurrence of ectopic Cushings syndrome or another PET syndrome. Deaths were categorized as ZES-related or non-ZES-related and classified into different causes. RESULTS Thirty-one percent of patients died, all of non-acid-related causes. One half died of a ZES-related cause; they differed from those who died of non-ZES deaths by having a large primary tumor, more frequently a pancreatic tumor; lymph node, liver, or bone metastases; ectopic Cushings syndrome; or higher gastrin levels. The extent of liver metastases correlated with survival rate. The presence of liver metastases alone only moderately decreased survival time; however, the additional development of bone metastases or ectopic Cushings syndrome markedly decreased survival rate. CONCLUSIONS In ZES, gastrinoma growth is now the main single determinant of long-term survival, with one half of patients dying a gastrinoma-related death and none an acid-related death. Large primary tumors that are pancreatic in location, the development of liver metastases, (especially if associated with bone metastases or Cushings syndrome), and the extent of liver metastases are all important prognostic factors. The identification of these factors allows the recognition of subgroups that can be used to tailor antitumor treatment approaches.

Zollinger-Ellison syndrome. Clinical presentation in 261 patients.

We prospectively evaluated the initial presenting symptoms in 261 patients with Zollinger-Ellison syndrome (ZES) over a 25-year period. Twenty-two percent of the patients had multiple endocrine neoplasia-type 1 (MEN-1) with ZES. Mean age at onset was 41.1 +/- 0.7 years, with MEN-1 patients presenting at a younger age than those with sporadic ZES (p < 0.0001). Three percent of the patients had onset of the disease < age 20 years, and 7% > 60 years. A mean delay to diagnosis of 5.2 +/- 0.4 years occurred in all patients. A shorter duration of symptoms was noted in female patients and in patients with liver metastases. Abdominal pain and diarrhea were the most common symptoms, present in 75% and 73% of patients, respectively. Heartburn and weight loss, which were uncommonly reported in early series, were present in 44% and 17% of patients, respectively. Gastrointestinal bleeding was the initial presentation in a quarter of the patients. Patients rarely presented with only 1 symptom (11%); pain and diarrhea was the most frequent combination, occurring in 55% of patients. An important presenting sign that should suggest ZES is prominent gastric body folds, which were noted on endoscopy in 94% of patients; however, esophageal stricture and duodenal or pyloric scarring, reported in numerous case reports, were noted in only 4%-10%. Patients with MEN-1 presented less frequently with pain and bleeding and more frequently with nephrolithiasis. Comparing the clinical presentation before the introduction of histamine H2-receptor antagonists (pre-1980, n = 36), after the introduction of histamine H2-receptor antagonists (1981-1989, n = 118), and after the introduction of proton pump inhibitors (PPIs) (> 1990, n = 106) demonstrates no change in age of onset; delay in diagnosis; frequency of pain, diarrhea, weight loss; or frequency of complications of severe peptic disease (bleeding, perforations, esophageal strictures, pyloric scarring). Since the introduction of histamine H2-receptor antagonists, fewer patients had a previous history of gastric acid-reducing surgery or total gastrectomy. Only 1 patient evaluated after 1980 had a total gastrectomy, and this was done in 1977. The location of the primary tumor in general had a minimal effect on the clinical presentation, causing no effect on the age at presentation, delay in diagnosis, frequency of nephrolithiasis, or severity of disease (strictures, perforations, peptic ulcers, pyloric scarring). Disease extent had a minimal effect on symptoms, with only bleeding being more frequent in patients with localized disease. Patients with advanced disease presented at a later age and with a shorter disease history (p = 0.001), were less likely to have MEN-1 (p = 0.0087), and tended to have diarrhea more frequently (p = 0.079). A correct diagnosis of ZES was made by the referring physician initially in only 3% of the patients. The most common misdiagnosis made were idiopathic peptic ulcer disease (71%), idiopathic gastroesophageal reflux disease (GERD) (7%), and chronic idiopathic diarrhea (7%). Other less common misdiagnosis were Crohn disease (2%) and various diarrhea diseases (celiac sprue [3%], irritable bowel syndrome [3%], infectious diarrhea [2%], and lactose intolerance [1%]). Other medical disorders were present in 55% of all patients; patients with sporadic disease had fewer other medical disorders than patients with MEN-1 (45% versus 90%, p < 0.00001). Hyperparathyroidism and a previous history of kidney stones were significantly more frequent in patients with MEN-1 than in those with sporadic ZES. Pulmonary disorders and other malignancies were also more common in patients with MEN-1. These results demonstrate that abdominal pain, diarrhea, and heartburn are the most common presenting symptoms in ZES and that heartburn and diarrhea are more common than previously reported. The presence of weight loss especially with abdominal pain, diarrhea, or heartburn is an important clue suggesting the presence of gastrinoma. The presence of prominent gastric body folds, a clinical sign that has not been appreciated, is another important clue to the diagnosis of ZES. Patients with MEN-1 presented at an earlier age; however, in general, the initial symptoms were similar to patients without MEN-1. Gastrinoma extent and location have minimal effects on the clinical presentation. Overall, neither the introduction of successful antisecretory therapy nor widespread publication about ZES, attempting to increase awareness, has shortened the delay in diagnosis or reduced the incidence of patients presenting with peptic complications. The introduction of successful antisecretory therapy, however, has dramatically decreased the rate of surgery in controlling the acid secretion and likely led to patients presenting with less severe symptoms and fewer complications. (ABSTRACT TRUNCATED)

ALVAC-SIV-gag-pol-env-Based Vaccination and Macaque Major Histocompatibility Complex Class I (A*01) Delay Simian Immunodeficiency Virus SIVmac-Induced Immunodeficiency

ABSTRACT T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4+ T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4+ T cells, and delayed disease progression following intrarectal challenge exposure of the animals to SIVmac251 (561). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8+ T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in Mamu-A*01-positive macaques following intravenous challenge with either SIVmac251 (561) or SIVSME660. However, a significant delay in CD4+ T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV89.6P or SHIVKU2, respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models.

Host defense molecule polymorphisms influence the risk for immune-mediated complications in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function in which defective superoxide production results in deficient microbicidal activity. CGD patients suffer from recurrent, life-threatening infections, and nearly half develop chronic gastrointestinal (GI) complications (colitis, gastric outlet obstruction, or perirectal abscess) and/or autoimmune/rheumatologic disorders (AIDs). To identify genetic modifiers of disease severity, we studied a cohort of 129 CGD patients, in whom seven candidate genes (myeloperoxidase [MPO], mannose binding lectin [MBL], Fcgamma receptors IIa, IIIa, IIIb, TNF-alpha, and IL-1 receptor antagonist), each containing a physiologically relevant polymorphism predicted to influence the host inflammatory response, were selected for analysis. Genotypes of MPO (P = 0.003) and FcgammaRIIIb (P = 0.007) were strongly associated with an increased risk for GI complications, while an FcgammaRIIa (P = 0.05) genotype was suggestive for an association. Patients with all three associated genotypes had the highest risk for GI complications (P < 0.0001). The risk of AIDs was strongly associated with variant alleles of MBL (P = 0.01) and weakly associated with an FcgammaRIIa genotype (P = 0.04). Patients with variant forms of both MBL and FcgammaRIIa had the highest risk of developing an AID (P = 0.003).

Vaccine-Elicited Antibodies Mediate Antibody-Dependent Cellular Cytotoxicity Correlated with Significantly Reduced Acute Viremia in Rhesus Macaques Challenged with SIVmac251

Effector cells armed with Abs can eliminate virus-infected target cells by Ab-dependent cellular cytotoxicity (ADCC), an immune mechanism that has been largely overlooked in HIV vaccine development. Here, we show that a prime/boost AIDS vaccine approach elicits potent ADCC activity correlating with protection against SIV in rhesus macaques (Macacca mulatta). Priming with replicating adenovirus type 5 host range mutant-SIV recombinants, followed by boosting with SIV gp120, elicited Abs with ADCC activity against SIVmac251-infected cells. In vitro ADCC activity correlated with in vivo reduced acute viremia after a mucosal challenge with pathogenic SIV. Our findings expose ADCC activity as an immune correlate that may be relevant in the rational design of an efficacious vaccine against HIV.