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Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration.

To determine the effects of IL-10 on cytokine and granulocyte responses during endotoxemia, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in combination with placebo injection, and once in conjunction with i.v. administered recombinant human IL-10 (rhIL-10) (25 microg/kg). In group 1, rhIL-10 was administered 2 min before endotoxin challenge; in group 2, the intervention was delayed for 1 h after endotoxin administration. rhIL-10 pretreatment reduced the LPS-induced rises in temperature and release of TNF, IL-6, IL-8, and IL-1 receptor antagonist. Endotoxin-induced granulocyte accumulation in lungs, as determined by dynamic granuloscintigrams, was prevented by rhIL-10 pretreatment, whereas granulocyte recruitment in liver and spleen was only modestly reduced. In addition, granulocyte degranulation, as measured by plasma elastase/alpha1-antitrypsin complexes, was blunted significantly by rhIL-10 pretreatment. Post-treatment with rhIL-10 did not influence LPS-induced temperature responses, cytokine release, or granulocyte degranulation. Both rhIL-10 pretreatment and post-treatment reduced LPS-induced cortisol levels. These results indicate that pretreatment with rhIL-10 reduces endotoxin-induced febrile responses, cytokine responses, and granulocyte accumulation in lungs, while in this acute model post-treatment with rhIL-10 exerts limited anti-inflammatory effects.

Adult↗

Immunotherapy with recombinant human interleukin-2 and recombinant interferon-alpha in lymphoma patients postautologous marrow or stem cell transplantation.

Immune-mediated effects appear to play a major role in controlling minimal residual disease (MRD). We, therefore, investigated the role of recombinant human interleukin-2 (rIL-2) given concomitantly with interferon-alpha (IFN-alpha) in malignant lymphoma (ML) patients with responding disease following autologous bone marrow or blood stem cell transplantation (ABSCT). Fifty-six patients were included in this investigation. Thirty-two patients had non-Hodgkin's lymphoma (NHL) and 24 patients had Hodgkin's disease (HD). Sixty-one patients (NHL 36, HD 25) served as historical controls. Patients from both groups had similar demographic characteristics, the same stage of disease at presentation, status of disease at transplantation, conditioning regimens, and type of transplant. rIL-2 and IFN-alpha were self-administered in two cycles beginning 2.5 to 10.5 months (median, 4 months) posttransplant and separated by a 4-week interval. Each cycle consisted of IFN-alpha subcutaneously (SC) 3 x 10(6) U/d x 5 d/wk combined with rIL-2 SC 3 to 6 IU/m2/d x 5 d/wk for 4 weeks. The incidence of survival and disease-free survival (DFS) was significantly higher in the group under investigation than in the historical controls (P < .01). Of 56 patients with ML treated with IFN-alpha + rIL-2, 45 patients are DFS (80.4%) after a follow-up of 7 to 78 months (median, 34 months), whereas in the historical controls, 32 of 61 (52.5%) patients are disease free, in a follow-up of 4 to 84 months (median, 23 months) posttransplant (P < .01). Our preliminary results are encouraging and suggest that home administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in ML patients with MRD following ABSCT.

Adolescent↗

Clinical trial of China-made recombinant streptokinase in acute myocardial infarction. Collaborative Study Group on Thrombolysis with China-made recombinant streptokinase.

OBJECTIVE: To evaluate the efficacy and safety of intravenous recombinant streptokinase (r-SK), produced in China, in the treatment of acute myocardial infarction (AMI). METHODS: One hundred and seventy-three patients with AMI admitted to seven hospitals from February to October 1995 were conformed to the inclusion and exclusion criteria of thrombolytic therapy. The patients were divided into two groups. One hundred and two patients in the Group A were randomized to receive r-SK (n = 51) or SK (n = 51). Seventy-one patients were treated with r-SK in the Group B. One and half million units of r-SK or SK were given intravenously over 60 minutes and the clinical criteria of reperfusion were evaluated. Coronary angiography was performed 90 minutes after thrombolytic therapy with r-SK in 34 patients and recanalization of infarct-related arteries was determined using the TIMI criteria. RESULTS: The reperfusion rate was 80.4% in 51 patients receiving r-SK and 74.5% in 51 patients receiving SK (P > 0. 05). The total reperfusion rate was 77.1% in 122 patients treated with r-SK. Ninety minutes after the initiation of thrombolytic therapy, the occluded infarct-related arteries were patent in 70. 6% (24/34) of patients treated with r-SK. Chill, hypotension and mild bleeding occurred respectively in 4.1%, 5.7% and 16.4% of patients with r-SK. CONCLUSION: China-made r-SK is a safe and effective thrombolytic agent.

Adult↗

Recombinant His-tagged DNA polymerase. II. Cloning and purification of Thermus aquaticus recombinant DNA polymerase (Stoffel fragment).

The Stoffel DNA fragment, shortened by 12 bp from 5' end, coding for Stoffel DNA polymerase (missing 4 amino acids at N-terminus of Stoffel amino-acids sequence) from the thermophilic Thermus aquaticus (strain YT-1) was amplified, cloned and expressed in Escherichia coli. The recombinant Stoffel fragment contained a polyhistidine tag at the N-terminus (21 additional amino acids) that allowed its single-step isolation by Ni2+ affinity chromatography. The enzyme was characterized and displayed high DNA polymerase activity and thermostability evidently higher than the native Taq DNA polymerase.

Amino Acid Sequence↗

Dose-response comparison of recombinant human nerve growth factor and recombinant human basic fibroblast growth factor in the fimbria fornix model of acute cholinergic degeneration.

Both nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) have been proposed for the treatment of Alzheimer's disease. This study describes a comparative, dose-response analysis of recombinant human (rh)NGF and rhbFGF in a rat unilateral fimbria-fornix model of acute cholinergic neuronal degeneration. Doses for rhNGF were 0.6, 6, 60, 600 and 1,800 ng/rat/day and for rhbFGF were 600, 1,800, 3,000 and 6,000 ng/rat/day, delivered for 4 weeks. The number of surviving septal cholinergic neurons was evaluated using ChAT immunohistochemistry. In control animals, the number of ChAT-positive neurons remaining on the lesioned side was between 22 and 18% compared to the non-lesioned side. Infusion with either neurotrophic factor increased the number of ChAT-positive neurons on the lesioned side in a dose-dependent manner. The maximal response to rhbFGF peaked at 3,000 ng/rat/day with a cell savings of 47%. However, there was evidence of neuropathological changes associated with rhbFGF. In contrast, rhNGF produced a maximal response with an infusion of 600 ng rhNGF/rat/day and a cell savings of 70% and no evidence of neuropathology, indicating that rhNGF was better tolerated and more efficacious than rhbFGF.

Acetylcholinesterase↗

Restoration of anti-interleukin-1 depressed natural killer activity by human recombinant interferon alpha or gamma, human recombinant interleukin-2 and indomethacin.

The lymphokines interleukin-2 and interferon alpha or gamma are synthesized and secreted by activated mononuclear cells (MC) and play a critical role in the proliferative expansion of T-lymphocyte effector cells during the immune response. The pretreatment of human peripheral blood mononuclear cells (PBMC) with antibody IgG against human interleukin-1 (IL-1) from normal rabbit serum, inhibited their natural killer (NK) activity against both myeloid (K562) and lymphoid (MOLT-4) cell lines. Percent specific lysis of tumor cells decreased by increasing the antibody anti-IL-1 dose in an almost linear fashion. When the effector cells were pretreated with human recombinant interleukin-2, human interferon alpha or gamma and indomethacin alone or in combination, the inhibitory effect of antibody against human IL-1 was almost totally reversed.

Cytotoxicity, Immunologic↗

Heterologous HIV-2 challenge of rhesus monkeys immunized with recombinant vaccinia viruses and purified recombinant HIV-2 proteins.

In an attempt to analyse the role of anti-envelope immunity in the protection of rhesus monkeys against an HIV-2 intravenous challenge, rhesus macaques were immunized twice with recombinant HIV-2 ROD vaccinia viruses (10(8) p.f.u. each) at days 0 and 30, followed by booster injections of purified HIV-2 proteins at months 8, 9, 15 and 27. One group of five macaques was immunized with the Gag, Pol, Vif and Nef antigens, whereas a second group received the same antigens with the addition of HIV-2 Env protein. Eight months after the last boost, the animals were challenged by intravenous injection of 100 AID50 of a monkey PBMC-grown stock of HIV-2 SBL. None of the animals was protected in spite of high humoral immune responses on day of challenge as determined by ELISA and Western Blot assays.

AIDS Vaccines↗

A randomized, multicenter study comparing the efficacy of recombinant FSH vs recombinant FSH with Ganirelix during superovulation/IUI therapy.

OBJECTIVE: The purpose of this study was to determine if use of a Gonadotropin releasing hormone (GnRH) antagonist, Ganirelix (Antagon), can improve pregnancy rates during superovulation with recombinant follicle-stimulating hormone (rFSH) followed by intrauterine insemination (IUI). STUDY DESIGN: This was a multicenter, prospective, randomized, open-label, assessor-blind, controlled trial of females (n = 54), ages 18 to 39 undergoing superovulation/IUI with up to 4 cycles of superovulation/IUI without Ganirelix (n = 66), or up to 4 cycles of superovulation/IUI with the addition of Ganirelix (n = 52). RESULTS: No statistically significant difference in clinical pregnancy rates per cycle initiated was found for patients in the treatment or control group (12% vs 7%, P =.29). Other variables assessed, including endometrial thickness, size of follicles, peak serum estradiol levels, mid-lutea progesterone levels, and total vials of rFSH used also showed no statistically significant difference. CONCLUSION: Superovulation/IUI cycles using Ganirelix produce similar pregnancy rates when compared with cycles not using a GnRH antagonist, although there is a trend towards better pregnancy rates in cycles with Ganirelix.

Adult↗

A catalytically active complex formed from the recombinant dI protein of Rhodospirillum rubrum transhydrogenase, and the recombinant dIII protein of the human enzyme.

Transhydrogenase is a proton pump. It has three components: dI and dIII protrude from the membrane and contain the binding sites for NAD(H) and NADP(H), respectively, and dII spans the membrane. We have expressed dIII from Homo sapiens transhydrogenase (hsdIII) in Escherichia coli. The purified protein was associated with stoichiometric amounts of NADP(H) bound to the catalytic site. The NADP+ and NADPH were released only slowly from the protein, supporting the suggestion that nucleotide-binding by dIII is regulated by the membrane-spanning dII. HsdIII formed a catalytically active complex with recombinant dI from Rhodospirillum rubrum (rrdI), even in the absence of dII. The rates of forward and reverse transhydrogenation catalysed by this complex are probably limited by slow release from dIII of NADPH and NADP+, respectively. The hybrid complex also catalysed high rates of 'cyclic' transhydrogenation, indicating that hydride transfer, and exchange of nucleotides with dI, are rapid. Stopped-flow experiments revealed a rapid, monoexponential, single-turnover burst of reverse transhydrogenation in pre-steady-state. The apparent first-order rate constant of the burst increased with the concentration of rrdI. A deuterium isotope effect (kH/kD approximately 2 at 27 degrees C) was observed when [4B-1H]NADPH was replaced with [4B-2H]NADPH. The characteristics of the burst of transhydrogenation with rrdI:hsdIII differed from those previously reported for rrdI:rrdIII (J.D. Venning et al., Eur. J. Biochem. 257 (1998) 202-209), but the differences are readily explained by a greater dissociation constant of the hybrid complex. The steady-state rate of reverse transhydrogenation by the rrdI:hsdIII complex was almost independent of pH, but there was a single apparent pKa ( approximately 9.1) associated with the cyclic reaction. The reactions of the dI:dIII complex probably proceed independently of those protonation/deprotonation reactions which, in the complete enzyme, are associated with H+ translocation.

Binding Sites↗

Comparative study of a whole-cell pertussis vaccine and a recombinant acellular pertussis vaccine. The Italian Multicenter Group for the Study of Recombinant Acellular Pertussis Vaccine.

The safety and immunogenicity of an acellular pertussis vaccine containing the genetically detoxified pertussis toxin PT-9K/129G, filamentous hemagglutinin, and pertactin, together with diphtheria and tetanus toxoids, were compared with those of a whole-cell pertussis component-diphtheria-tetanus vaccine. Four hundred eighty infants were enrolled into this prospective, multicenter, double-blind study. Each infant was randomly given three doses of one of the two vaccines at 2, 4, and 6 months of age. Both local and systemic adverse reactions, reported within 48 hours and 7 days of each injection, were less frequent after the acellular vaccine than after the whole-cell vaccine. The enzyme-linked immunosorbent assay titers to pertussis toxin, filamentous hemagglutinin, and pertactin, as well as the pertussis toxin-neutralizing titer measured by the Chinese hamster ovary cell assay, were significantly higher after the acellular vaccine was given. Both vaccines induced adequate levels of anti-diphtheria and anti-tetanus antibodies. We conclude that the recombinant acellular pertussis vaccine produces fewer reactions than the whole-cell vaccine and provides a high antibody response against the antigens of Bordetella pertussis involved in bacterial adhesion and systemic toxic effects.

Antibodies, Bacterial↗

Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Report from the European Cooperative Study Group for Recombinant Tissue-type Plasminogen Activator.

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Adult↗

Chemical inactivation of recombinant vaccinia viruses and the effects on antigenicity and immunogenicity of recombinant simian immunodeficiency virus envelope glycoproteins.

The efficiency of paraformaldehyde (PFA) and binary ethylenimine (BEI) in inactivating recombinant vaccinia virus (rVV), present in baby hamster kidney cells expressing simian immunodeficiency virus envelope glycoproteins (SIV-Env), was measured in a series of inactivation studies. Both compounds were shown to be effective in reducing rVV titres. The use of standard 3-day titration assays proved to be inadequate to measure PFA inactivation, since upon prolonged incubation, residual rVV infectivity was detected in cultures negative at 3 days. Different procedures using PFA or BEI were selected to assess their influence on the antigenicity and immunogenicity or rVV expressed SIV-Env. Antigenicity, as defined by the ability to react with a panel of monoclonal antibodies recognizing major antigenic sites, and immunogenicity, as defined by the ability to induce SIV envelope specific and virus neutralizing serum antibodies in rats, proved to be preserved after either inactivation procedure. These data show that both protocols using PFA or BEI can be used successfully as part of the procedures to remove residual rVV infectivity.

Animals↗

Use of recombinant FSH and recombinant LH in multiple follicular stimulation for IVF: a preliminary study.

Twelve patients (17 cycles) who needed >3000 IU of recombinant FSH (rFSH) on previous follicular stimulation attempts for IVF using rFSH (group A) underwent further attempts (a total of 12 cycles) using rFSH supplemented with rLH from day 7 of stimulation (group B). There was no significant difference in the total quantitative administration of rFSH (mean: 4759 versus 4800 IU rFSH), days of stimulation (14.0 versus 12.6), number of M2 oocytes per patient (3.76 versus 4.17) or embryo morphology between group A and group B respectively. However, there was a significant increase in the incidence of fertilization (60.9 versus 86.0%; P = 0.006) and clinical (ongoing) pregnancies (1 versus 6; P = 0.022). The higher incidence of fertilization increased the mean number of embryos transferred per patient, although in this small group the data was not significant (1.75 versus 2.71). This preliminary clinical trial suggests that in poor responders superimposing rLH upon a down-regulated cycle stimulated with rFSH improves relevant outcome data; and this preliminary trial has encouraged the need for a larger and more detailed study.

Journal Article↗

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Adolescent↗

Memory cytotoxic T lymphocyte responses in human immunodeficiency virus type 1 (HIV-1)-negative volunteers immunized with a recombinant canarypox expressing gp 160 of HIV-1 and boosted with a recombinant gp160.

A vaccine against human immunodeficiency virus (HIV) should induce virus-specific cytotoxic T lymphocyte (CTL) activity. Immunization of uninfected volunteers with a canarypox virus expressing HIV envelope was carried out in a phase I trial. Two injections of canarypox expressing HIV-1MN gp 160 (months 0 and 1) were followed by two boosts of recombinant envelope protein (months 3 and 6). HIV envelope-specific CTL were detected in peripheral blood mononuclear cells stimulated with autologous HIV-1-infected blast cells. T cell lines were obtained from 18 of 20 donors: CTL were detected at least once following immunization in 7 (39%) of these 18. This activity was mediated by major histocompatibility complex class I-restricted CD3+CD8+ T cells. For two subjects, this activity was still present 2 years after the initial immunization. The CTL responses with this prime-boost regimen are the best observed with any HIV vaccine tested in humans.

AIDS Vaccines↗

Recombinant lys-plasminogen given before, but not after, recombinant tissue-type plasminogen activator markedly improves coronary thrombolysis in dogs: relationship of thrombolytic efficacy with parameters of fibrinolysis.

Recombinant tissue-type plasminogen activator (rt-PA) administration rapidly restores blood flow in thrombosed coronary arteries, but coronary arteries often reocclude after initial thrombolysis. This occurs because of the short half-life of rt-PA and rapid increase in plasminogen activator inhibitor (PAI-1) and alpha2-antiplasmin levels in plasma. We hypothesized that administration of lys-plasminogen, which binds to fibrin with 10 times greater affinity and results in a loose fibrin structure (as compared with native glu-plasminogen), before rt-PA would enhance the thrombolytic efficacy of rt-PA and modulate parameters of fibrinolysis. To examine this hypothesis, dogs with electrically induced stable thrombus in the left anterior descending coronary artery (LAD) were treated with saline (group A, n = 9) or lys-plasminogen (group B, 2 mg/kg, n = 5), followed 10 min later by rt-PA (1 mg/kg in 20 min). Four other dogs with occlusive LAD thrombus were first given rt-PA, followed by lys-plasminogen (2 mg/kg) 50 min later (group C). Lys-plasminogen given before rt-PA restored flow in all dogs in 14 +/- 4 min (vs. 22 +/- 9 min in group A, p < 0.05), continuing > 2 h (vs. 41 +/- 15 min in group A, p < 0.02). Lys-plasminogen given after rt-PA did not potentiate the effect of rt-PA. Plasma t-PA antigen concentrations were highest in group B dogs at 2 h after rt-PA infusion. PAI-1 and alpha2-antiplasmin plasma levels were suppressed in all dogs receiving lys-plasminogen whether it was given before or after rt-PA. Therefore, lys-plasminogen given before rt-PA markedly potentiates the effect of rt-PA and alters the parameters of fibrinolysis. In contrast, lys-plasminogen given after rt-PA does not influence the thrombolytic effect of rt-PA, whereas it suppresses PAI-1 and alpha2-antiplasmin levels in plasma. This study also suggests that binding of plasminogen to the clot is more important than the plasma levels of PAI-1 and alpha2-antiplasmin.

Animals↗

The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis.

MSH4, a meiosis-specific member of the MutS-homolog family of genes, is required for normal levels of recombination and fertility in budding yeast, mouse, and Caenorhabditis elegans. In this paper, we report the identification and characterization of the Arabidopsis homolog of MSH4 (AtMSH4). We demonstrate that AtMSH4 expression can only be detected in floral tissues, consistent with a role in reproduction. Immunofluorescence studies indicate that its expression is limited to early meiotic prophase I, preceding the synapsis of homologous chromosomes. A T-DNA insertional mutant (Atmsh4) exhibited normal vegetative growth but a severe reduction in fertility, consistent with a meiotic defect; this was confirmed by cytological analysis of meiosis. RNAi-induced down-regulation of the MSH4 gene resulted in a similar fertility and meiotic phenotype. We demonstrate that prophase I chromosome synapsis is delayed and may be incomplete in Atmsh4, and metaphase I chiasma frequency is greatly reduced to approximately 15% of wild type, leading to univalence and nondisjunction. We show that these residual chiasmata are randomly distributed among cells and chromosomes. These features of chiasma frequency and distribution in Atmsh4 show close parallels to MSH4-independent crossovers in budding yeast that have been proposed to originate by a separate pathway. Furthermore, the characteristics of the MSH4-independent chiasmata in the Atmsh4 mutant closely parallel those of second-pathway crossovers that have been postulated from Arabidopsis crossover analysis and mathematical modeling. Taken together, this evidence strongly indicates that Arabidopsis possesses two crossover pathways.

Amino Acid Sequence↗

Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.

Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

Animals↗