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E Paoletti

Publications and source records attributed to E Paoletti.

At least 19 recordsLinked to original sources
PubMed2006

Photosynthetic responses to elevated CO(2) and O(3) in Quercus ilex leaves at a natural CO(2) spring.

Photosynthetic stimulation and stomatal conductance (Gs) depression in Quercus ilex leaves at a CO(2) spring suggested no down-regulation. The insensitivity of Gs to a CO(2) increase (from ambient 1500 to 2000 micromol mol(-1)) suggested stomatal acclimation. Both responses are likely adaptations to the special environment of CO(2) springs. At the CO(2)-enriched site, not at the control site, photosynthesis decreased 9% in leaves exposed to 2x ambient O(3) concentrations in branch enclosures, compared to controls in charcoal-filtered air. The stomatal density reduction at high CO(2) was one-third lower than the concomitant Gs reduction, so that the O(3) uptake per single stoma was lower than at ambient CO(2). No significant variation in monoterpene emission was measured. Higher trichome and mesophyll density were recorded at the CO(2)-enriched site, accounting for lower O(3) sensitivity. A long-term exposure to H(2)S, reflected by higher foliar S-content, and CO(2) might depress the antioxidant capacity of leaves close to the vent and increase their O(3) sensitivity.

Adaptation, Physiological↗
PubMed2006

Measuring, modelling and testing ozone exposure, flux and effects on vegetation in southern European conditions--what does not work? A review from Italy.

Ozone (O3) exposure at Italian background sites exceeds UN/ECE concentration-based critical levels (CLe(c)), if expressed in terms of AOT40. Yet the occurrence of adverse effects of O3 on forests and crops is controversial. Possible reasons include (i) ability of response indicators to provide an unbiased estimate of O3 effects, (ii) setting of current CLe(c) in terms of cut-off value and accumulation level, (iii) response functions adopted to infer a critical level, (iv) environmental limitation to O3 uptake and (v) inherent characteristics of Mediterranean vegetation. In particular, the two latter points suggest that critical levels based on accumulated stomatal flux (CLe(f)) can be a better predictor of O3 risk than CLe(c). While this concept is largely acknowledged, a number of factors may limit its applicability for routine monitoring. This paper reviews levels, uptake and vegetation response to O3 in Italy over recent years to discuss value, uncertainty and feasibility of different approaches to risk assessment.

Crops, Agricultural↗
PubMed2006

Comparison of calculated and measured foliar O3 flux in crop and forest species.

We designed a new gas exchange system that concurrently measures foliar H2O, O3, and CO2 flux (HOC flux system) while delivering known O3 concentrations. Stomatal responses of three species were tested: snapbean, and seedlings of California black oak (deciduous broadleaf) and blue oak (evergreen broadleaf). Acute O3 exposure (120-250 ppb over an hour) was applied under moderate light and low vapor pressure deficits during near steady state conditions. The rate of stomatal closure was measured when the whole plant was placed in the dark. An adjacent leaf on each plant was also concurrently measured in an O3-free cuvette. Under some conditions, direct measurements and calculated foliar O3 flux were within the same order of magnitude; however, endogenously low gs or O3 exposure-induced depression of gs resulted in an overestimation of calculated O3 fluxes compared with measured O3 fluxes. Sluggish stomata in response to light extinction with concurrent O3 exposure, and incomplete stomatal closure likewise underestimated measured O3 flux.

Carbon Dioxide↗
PubMed2006

Gravitational infusion of ethylenediurea (EDU) into trunks protected adult European ash trees (Fraxinus excelsior L.) from foliar ozone injury.

Adult ash trees (Fraxinus excelsior L.), known to be sensitive or insensitive to ozone, determined by presence or absence of foliar symptoms in previous years, were treated with ethylenediurea (EDU) at 450 ppm by gravitational trunk infusion on six occasions at 21-day intervals in summer 2005 at Turin, Italy. At the end of the season, foliar ozone injury on EDU-treated trees was not complete, but was greatly and significantly reduced when compared to results from trees infused with water. Significant symptom reduction occurred at any crown level in the treated trees suggesting that EDU protected whole crowns. Gravitational infusion of EDU resulted in protection from ozone injury for ozone-sensitive ash trees. The amount of EDU needed to provide protection is assumed to be in the range 13-26 mg m(-2) leaf.

Environmental Exposure↗
PubMed2006

Impact of ozone on Mediterranean forests: a review.

Ozone impact on Mediterranean forests remains largely under-investigated, despite strong photochemical activity and harmful effects on crops. As representative of O3 impacts on Mediterranean vegetation, this paper reviews the current knowledge about O3 and forests in Italy. The intermediate position between Africa and European mid-latitudes creates a complex patchwork of climate and vegetation. Available data from air quality monitoring stations and passive samplers suggest O3 levels regularly exceed the critical level (CL) for forests. In contrast, relationships between O3 exposure and effects (crown transparency, radial growth and foliar visible symptoms) often fail. Despite limitations in the study design or underestimation of the CL can also affect this discrepancy, the effects of site factors and plant ecology suggest Mediterranean forest vegetation is adapted to face oxidative stress, including O3. Implications for risk assessment (flux-based CL, level III, non-stomatal deposition) are discussed.

Adaptation, Physiological↗
PubMed2005

UV-B and Mediterranean forest species: direct effects and ecological consequences.

Experimental results from plants receiving elevated doses of UV-B radiation generally show that Mediterranean forest species are well protected against increases in UV-B radiation. Natural adaptations to water stress and excess light (elevated concentrations of UV-B screening compounds, leaf hairs, thick cuticle and epidermis), and UV-B responses (thickening of the cuticle, increase in carotenoids) may avoid or counter-balance UV-B radiation damage. This response confirms that Mediterranean forest vegetation is adapted to face oxidative stress factors, such as elevated tropospheric ozone concentrations, drought and high radiation, including UV-B. Nevertheless, in the long term, species-specific and season-specific differential responses in growth, physiology, phenology and reproductive behaviour may alter the interactions between species and lead to slow but important changes in ecosystem structure and function.

Acclimatization↗
PubMed2002

Arterial hypertension and left ventricular hypertrophy in hemodialysis patients.

The high prevalence of left ventricular hypertrophy (LVH) among hemodialysis patients may be a consequence of inadequate diagnosis and treatment of arterial hypertension (AH). AH is not adaquately controlled in hemodialysis patients probably due to an underestimation of the effective BP load due to the unreliability of clinical BP readings in this population. Furthermore, BP reduction induced by dialysis ultrafiltration is not an acceptable criterion for discontinuing antihypertensive therapy, particularly when LVH coexists. Indeed, the few available interventional studies have demonstrated that strict BP control, together with anemia correction and dialysis adequacy improvement, can induce significant regression of the LVH of hemodialysis patients. Moreover, the decrease of SBP, particularly as a result of ACE-inhibitor therapy, is the most important predictor of LVH regression. Finally the use of ABPM and of echocardiography are recommended for correctly detecting an underlying AH and for tailoring and monitoring the effectiveness of antihypertensive therapy in dialysis patients with LVH.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Inadequate diagnosis and therapy of arterial hypertension as causes of left ventricular hypertrophy in uremic dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in the dialyzed population, possibly because of inadequate diagnosis and therapy of arterial hypertension. The purpose of this study was to ascertain the adequacy of our approach in correctly identifying and treating arterial hypertension in our dialysis center. METHODS: Fifty-five dialyzed uremics were studied by continuous ambulatory blood pressure (BP) monitoring, which started before a single hemodialysis (HD) session, continued for 24 hours after HD ended, and was repeated for 15 minutes before the beginning of the next HD. Clinical pre-HD and post-HD routine BP measurements taken the month preceding BP monitoring were retrieved, and echocardiography was performed. RESULTS: LVH was present in 46 out of 55 patients, and clinical pre-HD arterial hypertension was present in 36 out of 55. There were discrepancies between clinical and monitored BPs, mostly concerning diastolic pre-HD BP since BP readings were lower than monitored BP records (P < 0.0002). Although both clinical and monitored BPs bore strong direct correlations with the left ventricular mass (LVM), the closest correlations were those for monitored BP. Four groups of patients were identified by BP monitoring: group A (N = 14), with persistently normal BP, and group D (N = 13), with persistently supranormal BP levels. There were also two other groups (group B, N = 19; and group C, N = 9), whose BP values were high before HD, normalized after HD, and then increased again either soon after HD (group C) or later on following HD (group B). Monthly averaged clinical pre-HD mean BP values differed significantly among the four groups [91 +/- 10 (SD) mm Hg in group A, 101 +/- 7 in group B, 106 +/- 6 in group C, and 106 +/- 7 in group D; P < 0.0001, analysis of variance], as did their corresponding LVMs [132 +/- 27 g/m2 body surface area (BSA), 156 +/- 26, 201 +/- 51, and 200 +/- 36; P < 0.0001]. There were also differences in dialytic age, which was significantly longer in group A patients (109 +/- 54 months), who also tended to have higher, although not significantly higher, Kt/V(urea) values. No differences, however, were detected among the groups as far as type, dosages, and number of antihypertensive drugs given to each individual patient. CONCLUSIONS: The high prevalence of LVH in the dialysis population might be the result of inadequate diagnosis and therapy of arterial hypertension. Arterial hypertension, in fact, was insufficiently treated in our dialysis center, since patients with varying degrees of severity of both arterial hypertension and LVH were kept on antihypertensive therapy of similar strength. Undertreatment may have resulted from not having recognized and/or from having underestimated the severity of arterial hypertension since some clinical BPs were measured incorrectly. Reluctance to use more aggressive antihypertensive therapy might also result from the deceptive feeling of "normalized" BP that one has following volume unloading with dialysis. This causes both the BP to run out of control between dialyses and LVH to worsen.

Adult↗
PubMed2000

Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 +/- 0. 25) than did i.n. immunization with NYVAC-HF (0.88 +/- 0.36; n = 9) and ALVAC-HF (0.61 +/- 0.43; n = 9, P = 3 x 10(-7)), and survival was also significantly better in the i.n.-parenteral group (3 of 9) than in the other HF-vaccinated animals (none of 18) or in controls immunized with RG (none of 5) (P = 0.0374). Multiple routes were not tested with the ALVAC vaccine. The results suggest that infant ferrets are less responsive to i.n. vaccination than are older ferrets and raises questions about the appropriateness of this route of immunization in infant ferrets or infants of other species.

Administration, Intranasal↗
PubMed1999

CD8+ lymphocyte antiviral activity in monkeys immunized with SIV recombinant poxvirus vaccines: potential role in vaccine efficacy.

Protection against intravenous simian immunodeficiency virus (SIV) challenge was assessed in rhesus macaques after immunization with a highly attenuated vaccinia (NYVAC)-SIV recombinant. One-third of vaccinated animals controlled viral infection and progressed to disease more slowly than control animals (Benson J, et al.: J Virol 1998;72:4170). However, this protection was not associated with neutralizing antibodies, cytotoxic T lymphocytes, or helper T cell responses. To explore other potential correlates of protection, we examined CD8+ T cell antiviral activity in macaques vaccinated with NYVAC-SIV, with or without added cytokine adjuvants, and in controls receiving only IL-12 or IL-12 plus IL-2. Before immunization, naive macaques exhibited a broad range of CD8+ T cell antiviral activity. Nevertheless, in the course of immunization, the vaccinated macaques as a group developed increased CD8+ T cell antiviral activity while the controls remained stable. Infectious SIV exposure also increased antiviral activity. Prechallenge antiviral activity levels of vaccinated macaques were not sufficient to prevent SIV transmission or control viral replication during acute infection. However, vaccinated animals consistently exhibited reduced viral loads postchallenge compared with controls. Moreover, high suppressive activity 8 weeks postchallenge, at which time the viremia set point was established, was significantly correlated with reduced viral load and slow disease progression. Prechallenge antiviral activity influenced this result, as decreased viremia and slow progressor status were more apparent in macaques with high suppressive activity both pre- and postchallenge. Our data demonstrate the impact of CD8+ antiviral activity on viral replication and disease progression, and suggest that vaccine designs able to elicit high levels of this activity will contribute significantly to protective efficacy.

Animals↗
PubMed1999

Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection.

Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein. Animals were challenged intranasally 4 weeks after the second vaccination with virulent CDV. Body weights, white blood cell (WBC) counts and temperatures were monitored and ferrets were observed daily for clinical signs of infection. WBCs were assayed for the presence of viral RNA by RT-PCR. Intranasally vaccinated animals survived challenge with no virologic or clinical evidence of infection. Vaccination by the intraduodenal route did not provide complete protection. All control animals developed typical distemper. Ferrets can be effectively protected against distemper by mucosal vaccination with poxvirus vaccines.

Animals↗
PubMed1998

Efficacy evaluation of prime-boost protocol: canarypoxvirus-based feline immunodeficiency virus (FIV) vaccine and inactivated FIV-infected cell vaccine against heterologous FIV challenge in cats.

OBJECTIVE: To evaluate the immunogenicity and prophylactic efficacy of immunization schemes employing a recombinant canarypoxvirus ('ALVAC')-based feline immunodeficiency virus (FIV) vaccine alone or in combination with an inactivated FIV-infected cell vaccine against homologous and heterologous FIV challenges in cats. METHODS: Specific pathogen-free cats were given a total of three immunizations with subtype A vaccines and challenged 4 weeks after the final immunization with 50 median animal infectious doses (ID50) of FIV-Petaluma, a subtype A isolate. Following the initial challenge, protected cats received a second challenge with 75 ID50 of FIV-Bangston, a subtype B isolate. FIV-specific humoral and cell-mediated responses were measured to determine the immune correlates of protection. RESULTS: Two of three cats immunized with the ALVAC FIV recombinants alone were protected from homologous FIV challenge in the presence of FIV-specific cytotoxic T-lymphocyte (CTL) responses but in the absence of FIV-specific humoral responses. All three cats immunized with the ALVAC-FIV recombinant and boosted with FIV-infected cell vaccine were also protected from homologous FIV challenge in the presence of both FIV-specific CTL and humoral responses. Partial to full protection was observed in ALVAC-FIV/FIV-infected cell vaccine-immunized cats against a heterologous FIV challenge given 8 months after the initial challenge. Two out of three cats had transient infection and the remaining cat had no sign of FIV infection at a dose at which all three control cats were readily infected. CONCLUSIONS: Immunization schemes employing ALVAC-based FIV vaccines in combination with inactivated FIV-infected cell vaccine generate protective immune responses that can cross-react with FIV isolates that are genetically distinct from the vaccine strains.

Animals↗
PubMed1998

Colon cancer cell vaccine prepared with replication-deficient vaccinia viruses encoding B7.1 and interleukin-2 induce antitumor response in syngeneic mice.

A replication-deficient recombinant vaccinia virus, NYVAC, was developed by deleting 18 open reading frames in the vaccinia virus genome. Recombinant NYVAC, encoding the murine T cell co-stimulatory gene B7.1 (CD 80) (NYVAC-B7.1) and the murine interleukin-2 gene (NYVAC-IL-2), were prepared and the expression of B7.1 and the secretion of IL-2 were respectively confirmed in vitro. The use of these viruses to prepare a potent tumor cell vaccine was studied in a syngeneic murine CC-36 colon adenocarcinoma model. Mice were immunized on days 1 and 8 with 10(6) irradiated CC-36 cells that were infected with 10(7) plaque-forming units of either NYVAC-B7.1, NYVAC-IL-2 or a control virus, NYVAC-HR, which encodes a vaccinia virus host-range gene. These mice were then challenged with 10(8) viable CC-36 tumor cells on day 15. All mice (10/10) in a group that had received no vaccination and all mice (20/20) in a group that had received a control vaccine of CC-36/NYVAC-HR developed tumor 4-weeks after tumor cell challenge. Interestingly, only 16/20 mice in a group that had received CC-36/ NYVAC-B7.1 showed the development of tumor after the same interval. The protection against tumor development and the reduction in tumor burden (as mean tumor diameter, 4 weeks after tumor challenge) were significant in this group when compared to groups that were either unvaccinated or vaccinated with CC-36/NYVAC-HR (mean tumor diameter = 6.51+/-3.2 mm compared to 26.5+/-0.9 mm or 26.2+/-1.8 mm respectively) (P = < 0.05). The protection against tumor in a group of mice that received CC-36/ NYVAC-IL-2 vaccination was similar to that in the unvaccinated group or the group receiving a CC-36/NYVAC-HR control vaccination. However, in a survival experiment, mice that received either CC36/NYVAC-B7.1 or CC-36/ NYVAC-IL-2 vaccination on the day of tumor transplantation survived significantly longer than mice that had not been vaccinated (median survival 60+ days, 60+ days or 23.5 days respectively) (P = < 0.05). Interestingly, when a therapeutic tumor vaccination was performed on day 4 after tumor transplantation, mice that had been vaccinated with either CC36/NYVAC-B7.1 or CC-36/NYVAC-IL-2 did not show an improved survival when compared to mice in the control that had not been vaccinated (median survival 28 days compared to 26 days or 25 days respectively). However, mice that had received a therapeutic vaccination with CC-36 cells infected with both NYVAC-B7.1 and NYVAC-IL-2, 4 days after tumor transplantation, survived significantly longer than control mice that had not received any vaccination (median survival 29.5 days compared to 25 days respectively) (P<0.05). These results suggest that a replication-deficient recombinant NYVAC encoding the B7.1 gene and NYVAC encoding the IL-2 gene can be used to produce an effective vaccinia-virus-augmented tumor cell vaccine.

Adenocarcinoma↗
PubMed1998

Angiotensin-converting enzyme gene polymorphism and reversibility of uremic left ventricular hypertrophy following long-term antihypertensive therapy.

BACKGROUND: Prolonged antihypertensive therapy might be less effective in reversing the left ventricular hypertrophy (LVH) in uremics bearing the deleted (DD) allele of the angiotensin converting enzyme (ACE) gene than in patients with the inserted (II) allele or in those heterozygous (ID) for the gene. METHODS: Thirteen DD and 17 II + ID hemodialyzed uremics were followed-up with yearly echocardiography and 24-hour blood pressure (BP) monitoring over five years while on an antihypertensive therapy that included ACE inhibitors as first line drugs. RESULTS: In the II + ID group there were significant decreases of the left ventricular mass index (LVMi) and of both systolic and diastolic BPs. These changes were less pronounced in the DD group, but the difference was not statistically significant given the wide overlap between the two groups. Further analysis of the data revealed that the only factor associated to a decreased LVMi was the decrease of the systolic BP irrespective of the ACE gene genotype of each individual patient. CONCLUSIONS: The ACE-gene genotype does not necessarily predict the extent to which LVMi will be lowered by ACE-inhibitors therapy. The LVH of hypertensive uremics is amenable by long-term antihypertensive therapy provided that it results in significantly decreased systolic blood pressure.

Adult↗
PubMed1998

Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group.

A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 microg of HIV-1SF2 recombinant (r) gp120 in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1MN and HIV-1SF2 neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion-inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway.

AIDS Vaccines↗
PubMed1998

Role of the vaccinia virus E3L and K3L gene products in rescue of VSV and EMCV from the effects of IFN-alpha.

Vaccinia virus (VV) has been shown to be relatively resistant to the antiviral effects of interferon-alpha (IFN-alpha) and to rescue replication of IFN-sensitive viruses, such as encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV), from the antiviral effects of IFN. The E3L and K3L gene products have been implicated in the IFN resistance of VV. We have investigated the role that these VV-encoded functions play in the rescue of VSV and EMCV from the effects of IFN. Transient expression of the E3L open reading frame (ORF) was sufficient to rescue VSV but not EMCV from the IFN-induced antiviral state. Rescue of VSV by mutants of E3L correlated with the ability of the mutated E3L gene products to bind dsRNA. Conversely, transient expression of the K3L ORF was sufficient to partially rescue EMCV but not VSV from the effects of IFN. Results with VV deleted of either the K3L or E3L ORFs were consistent with results obtained by transient expression of these genes. These results demonstrate that the VV E3L gene products are likely responsible for the VV-mediated rescue of VSV from the effects of IFN and the K3L gene product is likely at least partly responsible for rescue of EMCV.

Antiviral Agents↗
PubMed1998

Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIV(mac251): dependence on route of challenge exposure.

Vaccine protection from infection and/or disease induced by highly pathogenic simian immunodeficiency virus (SIV) strain SIV(mac251) in the rhesus macaque model is a challenging task. Thus far, the only approach that has been reported to protect a fraction of macaques from infection following intravenous challenge with SIV(mac251) was the use of a live attenuated SIV vaccine. In the present study, the gag, pol, and env genes of SIV(K6W) were expressed in the NYVAC vector, a genetically engineered derivative of the vaccinia virus Copenhagen strain that displays a highly attenuated phenotype in humans. In addition, the genes for the alpha and beta chains of interleukin-12 (IL-12), as well as the IL-2 gene, were expressed in separate NYVAC vectors and inoculated intramuscularly, in conjunction with or separate from the NYVAC-SIV vaccine, in 40 macaques. The overall cytotoxic T-lymphocyte (CTL) response was greater, at the expense of proliferative and humoral responses, in animals immunized with NYVAC-SIV and NYVAC-IL-12 than in animals immunized with the NYVAC-SIV vaccine alone. At the end of the immunization regimen, half of the animals were challenged with SIV(mac251) by the intravenous route and the other half were exposed to SIV(mac251) intrarectally. Significantly, five of the eleven vaccinees exposed mucosally to SIV(mac251) showed a transient peak of viremia 1 week after viral challenge and subsequently appeared to clear viral infection. In contrast, all 12 animals inoculated intravenously became infected, but 5 to 6 months after viral challenge, 4 animals were able to control viral expression and appeared to progress to disease more slowly than control animals. Protection did not appear to be associated with any of the measured immunological parameters. Further modulation of immune responses by coadministration of NYVAC-cytokine recombinants did not appear to influence the outcome of viral challenge. The fact that the NYVAC-SIV recombinant vaccine appears to be effective per se in the animal model that best mirrors human AIDS supports the idea that the development of a highly attenuated poxvirus-based vaccine candidate can be a valuable approach to significantly decrease the spread of human immunodeficiency virus (HIV) infection by the mucosal route.

Animals↗