Immediate Nasal Reconstruction in Management of Infected Nasal Alloplast and Allografts: A Case Series.

BACKGROUND: The use of alloplastic and allogenic nasal implants is widely popular in rhinoplasty. However, the use of these materials is accompanied by a risk of infection and extrusion. Traditionally, management of these complications is performed in a dual-staged fashion. First, the implant is removed and infection is controlled, then a delayed reconstruction is performed. However, scarring and soft tissue contracture make a delayed reconstruction challenging, and optimal aesthetic outcomes are difficult to achieve. This study was designed to evaluate the outcomes of immediate nasal reconstruction following removal of an infected nasal implant. METHODS: A retrospective chart review was performed of all patients who had infected nasal implants and underwent simultaneous removal and immediate nasal reconstruction with autologous cartilages (n = 8). Data collected included patient age, race, pre-operative presentation, intraoperative surgical maneuvers, and post-operative outcomes and complications. Post-operative results were used to measure success of the single-staged method. RESULTS: Follow-up ranged from 12 to 156 months with mean 84.4 months of the eight patients who were evaluated in the study, none had any major post-operative complications that required revision or reconstruction. All of the patients had marked improvement in nasal form and function. Six of the eight (75%) patients reported excellent aesthetic outcomes; two (25%) requested revisional surgeries for aesthetic concerns. CONCLUSION: Low complication rates and excellent aesthetic outcomes are possible in immediate autologous reconstruction following removal of an infected nasal implant. This is an alternative approach that obviates the inherent problems of a traditional delayed reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ..

Dorsal Augmentation.

To manage the deficient nasal dorsum, a thorough knowledge of dorsal augmentation techniques should be mastered by the rhinoplasty specialist. Indications for dorsal augmentation may arise in both primary and revision rhinoplasty presentations. To direct operative planning, a complete facial analysis, noting the importance of maintaining overall nasofacial balance, is essential. An array of techniques, including autologous and nonautologous (ie, allogeneic and synthetic) sources, have been used globally-each carrying its own advantages and disadvantages. The authors believe autologous grafts to be the optimal source for dorsal augmentation because of their biocompatibility and ability to produce natural and long-lasting outcomes.

Rhinosurgery during and after the COVID-19 Pandemic: International Consensus Conference Statement on Preliminary Perioperative Safety Measures.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic has widely affected rhinosurgery, given the high risk of contagion and the elective nature of the aesthetic procedure, generating many questions on how to ensure safety. The Science and Research Committee of the Rhinoplasty Society of Europe aimed at preparing consensus recommendations on safe rhinosurgery in general during the COVID-19 pandemic by appointing an international panel of experts also including delegates of The Rhinoplasty Society. METHODS: A Zoom meeting was performed with a panel of 14 international leading experts in rhinosurgery. During 3.5 hours, four categories of questions on preoperative safety measures in private practice and outpatient clinics, patient assessment before and during surgery, and legal issues were presented by four chairs and discussed by the expert group. Afterward, the panelists were requested to express an online, electronic vote on each category and question. The panel's recommendations were based on current evidence and expert opinions. The resulting report was circulated in an iterative open e-mail process until consensus was obtained. RESULTS: Consensus was obtained in several important points on how to safely restart performing rhinosurgery in general. Preliminary recommendations with different levels of agreement were prepared and condensed in a bundle of safety measures. CONCLUSION: The implementation of the panel's recommendations may improve safety of rhinoplasty by avoiding operating on nondetected COVID-19 patients and minimizing severe acute respiratory syndrome coronavirus 2 virus spread in outpatient clinics and operating rooms.

Assessment of the Impact of the Recombinant Porcine Reproductive and Respiratory Syndrome Virus Horsens Strain on the Reproductive Performance in Pregnant Sows.

This study assessed the impact of a PRRSV (porcine reproductive and respiratory syndrome virus) recombinant strain (Horsens strain) on the reproductive performance of naïve pregnant sows in the last third of gestation. Fifteen sows were included: four negative reproductive controls (NTX), five infected with a PRRSV-1 field strain (Olot/91, T01), and six infected with the recombinant PRRSV-1 strain (Horsens strain, T02). Piglets were monitored until weaning. Reproductive performance was the primary variable. In sows, viremia and nasal shedding (T01 and T02 groups), and, in piglets, viral load in blood and in lungs, as well as macroscopic lung lesions (T01 and T02 groups), were the secondary variables. The reproductive performance results were numerically different between the two challenged groups. Moreover, viral loads in blood were 1.83 × 106 ± 9.05 × 106 copies/mL at farrowing, 1.05 × 107 ± 2.21 × 107 copies/mL at weaning from piglets born from T01 animals and 1.64 × 103 ± 7.62 × 103 copies/mL at farrowing, 1.95 × 103 ± 1.17 × 104 copies/mL at weaning from piglets born from T02 sows. Overall, 68.8% of T01 piglets and 38.1% of T02 piglets presented mild lung lesions. In conclusion, the results suggest that Horsens strain is less virulent than the field strain Olot/91 under these experimental conditions.

Construction and efficacy evaluation of novel swine leukocyte antigen (SLA) class I and class II allele-specific poly-T cell epitope vaccines against porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important global swine disease. Here we report the development of subunit PRRSV-2 vaccines by expressing swine leucocyte antigen (SLA) class I and class II allele-specific epitope antigens in a robust adenovirus vector. SLA I-specific CD8 and SLA II-specific CD4 T cell epitopes of PRRSV-2 NADC20 were predicted in silico. Stable murine leukaemia cell lines (RMA-S), which are TAP-deficient and lacking endogenous class I epitope loading, were established to express different SLA I alleles. The binding stability of PRRSV T cell epitope peptides with SLA I alleles expressed on RMA-S cells was characterized. Two PRRSV poly-T cell epitope peptides were designed. NADC20-PP1 included 39 class I epitopes, consisting of 8 top-ranked epitopes specific to each of 5 SLA I alleles, and fused to 5 class II epitopes specific to SLA II alleles. NADC20-PP2, a subset of PP1, included two top-ranked class I epitopes specific to each of the five SLA I alleles. Two vaccine candidates, Ad-NADC20-PP1 and Ad-NADC20-PP2, were constructed by expressing the polytope peptides in a replication-incompetent human adenovirus 5 vector. A vaccination and challenge study in 30 piglets showed that animals vaccinated with the vaccines had numerically lower gross and histopathology lung lesions, and numerically lower PRRSV RNA loads in lung and serum after challenge compared to the controls, although there was no statistical significance. The results suggested that the Ad-NADC20-PP1 and Ad-NADC20-PP2 vaccines provided little or no protection, further highlighting the tremendous challenges faced in developing an effective subunit PRRSV-2 vaccine.

Assessment of Wellbeing and Anxiety-related Disorders in Those Seeking Rhinoplasty: A Crowdsourcing-based Study.

BACKGROUND: Recently, it has been proposed that psychosocial concerns may motivate the demand for aesthetic rhinoplasty. Although successful operations often improve the quality of life and self-esteem symptoms in patients with sound mental health, they may actually result in unsatisfactory outcomes in those patients with significant depression, anxiety, or other severe psychological disorders. The purpose of this study was to assess the incidence of psychological disorders in patients seeking rhinoplasty. METHODS: A prospective cross-sectional study of 298 random volunteers was conducted, with each participant completing a survey instrument that was administered through an internet crowd-sourcing service (Amazon Mechanical Turk). Participants were asked to complete a 10-item standardized SHNOS scale, and a 26-question PRIME-MD questionnaire in order to assess functional and aesthetic need for rhinoplasty, and the incidence of psychological disorders respectively. RESULTS: 38.95% of female participants reported a willingness to undergo aesthetic rhinoplasty, with a significantly lower number of men reporting the same (27.78%, P = 0.042). Adults between the ages of 18-24 (52.92%) were more willing to undergo aesthetic rhinoplasty, as compared to any other age group (P < 0.01). It was found that 57.84% of patients interested in surgery reported a psychological disorder as determined by the PRIME-MD questionnaire. CONCLUSIONS: Those suffering from major depressive disorder, generalized anxiety disorder, or body dysmorphic disorder may seek aesthetic rhinoplasty as a solution. It is important that surgeons assess patient mental health prior to treatment in order to avoid unsuccessful outcomes secondary to psychosocial illness.

Porcine circovirus type 2a or 2b based experimental vaccines provide protection against PCV2d/porcine parvovirus 2 co-challenge.

With the discovery of Porcine circovirus type 2d (PCV2d) in the USA in 2012 and subsequent genotype shift from the previously predominant PCV2b to PCV2d in the face of widespread PCV2a vaccination, concerns over PCV2 vaccine efficacy were raised. The objective of this study was to evaluate the efficacy of two similarly produced PCV2 vaccines, one containing the PCV2a capsid and the other one containing the PCV2b capsid, in the conventional pig model against PCV2d/porcine parvovirus 2 (PPV2) co-challenge. A co-challenge was added since there is evidence that PPV2 may exacerbate PCV2 infection and since PCV2 only rarely causes disease in experimentally infected pigs, hence vaccine efficacy can be difficult to assess. In brief, sixty 3-week-old-pigs from a PCV2 seropositive farm without evidence of active virus replication (no PCV2 viremia, low antibody titers with no evidence of increase after two consecutive bleedings) were blocked by PCV2 antibody titer and then randomly divided into three groups with 20 pigs each, a non-vaccinated group (challenge control), a PCV2a vaccinated group (VAC2a) and a PCV2b vaccinated group (VAC2b). Vaccinations were done at 4 and again at 6 weeks of age. At 8 weeks of age, all pigs were challenged with a PCV2d strain via intranasal and intramuscular routes of inoculation followed by intramuscular administration of PPV2 one day later. PCV2 vaccination, regardless of PCV2 genotype, resulted in significantly higher humoral and cellular immunity compared to non-vaccinated challenge control pigs as evidenced by increased numbers of interferon (IFN) γ secreting cells after PCV2d stimulation of peripheral blood mononuclear cells collected prior to challenge. Furthermore, PCV2a and PCV2b vaccinations both reduced PCV2d viremia and PCV2-associated pathological lesions. Under the study conditions, the PCV2a and PCV2b vaccine preparations each induced immune responses and clinical protection against a heterologous PCV2d/PPV2 co-challenge.

Autologous Costal Cartilage Harvest for Rhinoplasty with Simultaneous Breast Surgery: A Safe and Efficient Technique.

BACKGROUND: Autologous costal cartilage is frequently required for revision rhinoplasties and for challenging primary rhinoplasties. Patients undergoing a concomitant breast surgery can have costal cartilage harvested through their breast surgery incisions, thereby obviating an additional rib harvest scar. The safety and efficacy of this approach has yet to be described. OBJECTIVES: The aim of this study was to evaluate the outcomes, safety, and results of a new technique, described here, for harvesting costal cartilage during a concomitant breast operation. Specifically, the rates of capsular contracture and rhinoplasty revisions were of great interest. METHODS: A retrospective review was performed evaluating the senior author's experience with this technique. Data collected included patient demographics, operations performed, operative time, perioperative morbidity, and postoperative complications. Rates of capsular contracture and rhinoplasty revisions were compared with national averages. RESULTS: A total of 31 female patients were included. Ten (32.3%) breast complications occurred. There were 6 (19.4%) rhinoplasty complications, comprising 1 infection and 5 revisions. The capsular contracture rate was 6% and the rhinoplasty revision rate was 16%. Both of these rates are comparable to independent breast surgeries and rhinoplasties. There were no cases of perioperative mortality or major morbidity. CONCLUSIONS: Combining breast surgery and rhinoplasty surgery allows for autologous rib harvest through the breast surgery incisions. This is a safe technique that results in outcomes similar to either procedure performed alone. In addition, the patient is spared an additional surgery and donor site scar.

Cytotoxic T lymphocyte epitopes identified from a contemporary strain of porcine reproductive and respiratory syndrome virus enhance CD4+CD8+ T, CD8+ T, and γδ T cell responses.

Immuno-stimulatory class I-restricted cytotoxic T lymphocytes (CTL) epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) are important for vaccine development. In this study we first determined the expression frequency of swine leukocyte antigen (SLA) class I alleles in commercial pigs in the United States. The SLA genotyping result allowed us to predict potential CTL epitopes from a contemporary strain of PRRSV (RFLP 1-7-4) by using bioinformatic tools. The predicted epitopes were then evaluated in an ex vivo stimulation assay with peripheral blood mononuclear cells isolated from pigs experimentally-infected with PRRSV. Using flow-cytometry analysis, we identified a number of immuno-stimulatory CTL epitopes, including two peptides from GP3 and two from Nsp9 that significantly improved both degranulation marker CD107a and IFN-γ production in cytotoxic CD4+CD8+ T cells, CD8+ T cells, and γδ T cells, and two peptides that inhibited IFN-γ production. These CTL epitopes will aid future vaccine development against PRRSV.

Immune response development after vaccination of 1-day-old naïve pigs with a Porcine Reproductive and Respiratory Syndrome 1-based modified live virus vaccine.

BACKGROUND: The development of the innate and adaptive immune responses to Porcine reproductive and respiratory syndrome virus (PRRSV) after vaccination of 1 day-old pigs with a PRRSV-1 based modified live virus (MLV) vaccine by intramuscular (IM) and intranasal (IN) routes was characterised, before and after challenge with a heterologous PRRSV-1 isolate at 18 weeks post-vaccination. Twenty-five PRRSV-seronegative piglets were used. At 1 day of age, pigs were administered with a single dose of vaccine via the IM (n = 10) or the IN route (n = 10). Control group (n = 5) received saline solution. After vaccination, pigs were bled at days 3, 7, 28, 56, 83, 113 and 125. Levels of cytokines IL-10, IL-8, IFN-α (measured by ELISA tests of serum), TNF-α and IFN-γ (measured by ELISA and ELISPOT, respectively, from stimulated peripheral blood mononuclear cells), and serum neutralising antibodies (NA) to the vaccine strain, were measured. RESULTS: The induction of IL-10 was rare, indicating that IL-10 mediated immunomodulation/immune dysfunction was not a feature of this vaccine or of the challenge virus. IL-8 was detected in only two pigs following vaccination, but in the majority of pigs after challenge, indicating that their ability to produce an innate immune response was not impaired. TNF-α was not detected in any vaccinated pigs until day 83. After challenge, only a minority of pigs produced TNF-α. IFN-α was detected in all vaccinated pigs following vaccination, indicating the potential for development of an effective Th1 adaptive immune response. IFN-γ-secreting cells were detected in all vaccinated pigs after vaccination. NA to the vaccine strain were first detected at day 56 in pigs vaccinated by both routes, and remained at similar levels until challenge. After challenge, a boost in NA was observed. The efficacy of the vaccine was demonstrated by reduction of viraemia and nasal shedding after challenge. CONCLUSIONS: The administration of a PRRSV-1 based MLV vaccine to 1 day-old piglets was able to induce an immune response characterised by: (1) undetectable or low levels of IL-10, IL-8 and TNF-α, (2) an increase in IFN-α expression within the first seven days, (3) a gradual increase in the number of antigen-specific IFN-γ-secreting cells, and (4) induction of detectable NA. After challenge with a heterologous strain, there was a rapid boost in NA titres, indicating a priming effect of the vaccine.

Dynamic occupancy modeling of temperate marine fish in area-based closures.

Species distribution models (SDMs) are commonly used to model the spatial structure of species in the marine environment, however, most fail to account for detectability of the target species. This can result in underestimates of occupancy, where nondetection is conflated with absence. The site occupancy model (SOM) overcomes this failure by treating occupancy as a latent variable of the model and incorporates a detection submodel to account for variability in detection rates. These have rarely been applied in the context of marine fish and never for the multiseason dynamic occupancy model (DOM). In this study, a DOM is developed for a designated species of concern, cusk (Brosme brosme), over a four-season period. Making novel use of a high-resolution 3-dimensional hydrodynamic model, detectability of cusk is considered as a function of current speed and algae cover. Algal cover on the seabed is measured from video surveys to divide the study area into two distinct regions: those with canopy forming species of algae and those without (henceforth bottom types). Modeled estimates of the proportion of sites occupied in each season are 0.88, 0.45, 0.74, and 0.83. These are significantly greater than the proportion of occupied sites measured from underwater video observations which are 0.57, 0.28, 0.43, and 0.57. Individual fish are detected more frequently with increasing current speed in areas lacking canopy and less frequently with increasing current speed in areas with canopy. The results indicate that, where possible, SDM studies for all marine species should take account of detectability to avoid underestimating the proportion of sites occupied at a given study area. Sampling closed areas or areas of conservation often requires the use of nonphysical, low impact sampling methods like camera surveys. These methods inherently result in detection probabilities less than one, an issue compounded by time-varying features of the environment that are rarely accounted for marine studies. This work highlights the use of modeled hydrodynamics as a tool to correct some of this imbalance.

Vaccination of 1-day-old pigs with a porcine reproductive and respiratory syndrome virus (PRRSV) modified live attenuated virus vaccine is able to overcome maternal immunity.

BACKGROUND: The objective of the study was to evaluate the influence of maternally derived antibodies (MDA) on the efficacy of a PRRSV-1 based attenuated vaccine, when administered in 1 day-old piglets by the intramuscular route. The protective immunity of the modified live virus vaccine was evaluated in pigs born from seropositive sows, vaccinated at 1 day of age, upon inoculation with a PRRSV-1 isolate. The animals were challenged when the levels of MDAs detected by seroneutralization test (SNT) in the non-vaccinated control group became undetectable (10 weeks after vaccination). RESULTS: A protective effect of vaccination was observed since a significant reduction of viral load in serum compared to the control group was detected in all sampling days after challenge; efficacy was supported by the significant reduction of nasal and oral shedding as well as in rectal temperatures. Clinical signs were not expected after the inoculation of a PRRSV-1 subtype 1 challenge strain. However, the challenge virus was able to develop fever in 61% of the control pigs. Vaccination had a positive impact on rectal temperatures since the percentage of pigs that had fever at least once after challenge was reduced to 31% in vaccinated animals, and control pigs had significantly higher rectal temperatures than vaccinated pigs 3 days post-challenge. The lack of a vaccination effect in body weight gain was probably due to the short evaluation period after challenge (10 days). In the vaccinated group, 9/16 pigs (56%) experienced an increase in ELISA S/P ratio from the day of vaccination to 67 days post-vaccination. All vaccinated pigs were seropositive before challenge, indicating the development of an antibody response following vaccination even in the face of MDAs. In contrast to ELISA results, only 2/16 vaccinated pigs developed neutralizing antibodies detectable by a SNT that used a subtype 1 MA-104 adapted strain. Even in the absence of SN antibodies, vaccinated pigs were protected from challenge with a heterologous strain. The role of cell-mediated immunity should be considered, if protection was not mediated by SN antibodies only. CONCLUSIONS: The efficacy of the attenuated PRRSV-1 vaccine in 1-day-old pigs seropositive to PRRSV prior to a PRRSV-1 challenge was demonstrated by improvement of clinical, virological and immunological variables. With the current experimental design, maternal immunity did not interfere with the development of a protective immune response against a PRRSV-1 challenge, after vaccination of 1 day-old pigs. Confirmation of these results under field conditions will be needed.

Porcine Mesothelium-Wrapped Diced Cartilage Grafts for Nasal Reconstruction.

BACKGROUND: Fascia-wrapped diced cartilage grafts have become a useful tool in modern rhinoplasty surgery. Unfortunately, fascial harvest is associated with donor site morbidity; therefore, a nonautologous alternative to fascia would be ideal. Decellularized porcine mesothelium (PM), Meso BioMatrix™, is an acellular scaffold that could potentially fill this need. To determine if PM could serve as an acceptable alternative, we histologically compared diced cartilage grafts wrapped in fascia versus PM. METHODS: Human rib cartilage and temporoparietal fascia were obtained under an IRB-approved protocol. Cartilage was diced into 0.5 mm pieces and implanted in subcutaneous pockets in nude rats. Implanted materials included cartilage alone, cartilage wrapped in fascia, cartilage wrapped in PM, fascia alone, or PM alone. Specimens were harvested at 8 weeks and stained with hematoxylin and eosin, Masson's trichrome, Safranin-O, and Verhoeff's stain to assess cartilage viability, architecture, and regenerative potential. RESULTS: Unwrapped diced cartilage showed the highest cartilage viability, but was associated with loss of contour and dispersion of the cartilage pieces. Meso BioMatrix-wrapped grafts maintained contour and cartilage pieces had not dispersed; however, there was a significantly lower number of nucleated lacunae and a greater amount of basophilia than both fascia-wrapped cartilage and unwrapped cartilage. There was no significant difference in cartilage resorption between fascia-wrapped cartilage and Meso BioMatrix-wrapped cartilage or in the proteoglycan or collagen content between all groups. CONCLUSION: Off-the-shelf decellularized PM was associated with lower cartilage viability than unprocessed fascial allograft. No cartilage piece dispersion, fibrosis, resorption, or a foreign body reaction to Meso BioMatrix was observed. PM, although not equivalent to autologous tissue, may be utilized to achieve acceptable clinical results and be a viable alternative that limits donor side morbidity. This experimental study supports further clinical investigation of this material in rhinoplasty procedures.

Evidence-Based Medicine: Current Practices in Rhinoplasty.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Perform aesthetic and functional nasal analysis to guide septorhinoplasty. 2. Recognize common complications associated with rhinoplasty. 3. Select appropriate septorhinoplasty techniques to refine nasal aesthetics and treat nasal airway obstruction. 4. Identify factors leading to poor patient satisfaction following rhinoplasty. SUMMARY: Septorhinoplasty is among the most technically challenging procedures in the realm of plastic and reconstructive surgery. Moreover, it is a constantly evolving topic with extensive background literature. Surgeons must be comfortable with the traditional knowledge base and the current practices in the field. This article reviews the latest thinking on patient selection, functional indications, aesthetic analysis, and operative techniques in septorhinoplasty, with an emphasis on key cartilage grafting and tip suture techniques.

Vaccination against porcine reproductive and respiratory syndrome virus (PRRSV) reduces the magnitude and duration of viremia following challenge with a virulent heterologous field strain.

Forty PRRS-negative, three week-old weaned pigs were randomized into two groups in separate rooms and inoculated with a modified live PRRS vaccine (Fostera® PRRS) or control (PBS). Four weeks after vaccination pigs were rehoused in a single room and challenged intranasally and intramuscularly with virulent PRRSV strain NADC20. Timed serum samples were collected and titrated for PRRS virus and anti-PRRS virus antibodies. The study concluded when ≥80% of the pigs in the control group were determined to be virus negative (27days post-challenge). Mean duration of viremia was significantly lower (p=0.0327) for vaccinated pigs compared to non-vaccinated pigs. A significant reduction (p≤0.0053) in mean post-challenge viremia titer was seen in vaccinates compared to non-vaccinates from days 8 through 22 post-challenge. At the individual pig level, no pigs in the vaccinated group had detectible PRRSV in serum at the end of the study (27days post-challenge), while 15% of non-vaccinated pigs remained positive for virus.

Chimeric porcine reproductive and respiratory syndrome virus containing shuffled multiple envelope genes confers cross-protection in pigs.

The extensive genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) strains is a major obstacle for vaccine development. We previously demonstrated that chimeric PRRSVs in which a single envelope gene (ORF3, ORF4, ORF5 or ORF6) was shuffled via DNA shuffling had an improved heterologous cross-neutralizing ability. In this study, we incorporate all of the individually-shuffled envelope genes together in different combinations into an infectious clone backbone of PRRSV MLV Fostera(®) PRRS. Five viable progeny chimeric viruses were rescued, and their growth characteristics were characterized in vitro. In a pilot pig study, two chimeric viruses (FV-SPDS-VR2,FV-SPDS-VR5) were found to induce cross-neutralizing antibodies against heterologous strains. A subsequent vaccination/challenge study in 72 pigs revealed that chimeric virus FV-SPDS-VR2 and parental virus conferred partial cross-protection when challenged with heterologous strains NADC20 or MN184B. The results have important implications for future development of an effective PRRSV vaccine that confers heterologous protection.

Live porcine reproductive and respiratory syndrome virus vaccines: Current status and future direction.

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980s. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990s, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork producers and biologics companies.

Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: Current status and future direction.

Within a few years of its emergence in the late 1980s, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely used, but have failed to provide complete protection against emerging and heterologous field strains of the virus. Moreover, like many other MLVs, PRRSV-MLVs have safety concerns including vertical and horizontal transmission of the vaccine virus and several documented incidences of reversion to virulence. Thus, the development of efficacious inactivated vaccines is warranted for the control and eradication of PRRS. Since the early 1990s, researchers have been attempting to develop inactivated PRRSV vaccines, but most of the candidates have failed to elicit protective immunity even against homologous virus challenge. Recent research findings relating to both inactivated and subunit candidate PRRSV vaccines have shown promise, but they need to be pursued further to improve their heterologous efficacy and cost-effectiveness before considering commercialization. In this comprehensive review, we provide information on attempts to develop PRRSV inactivated and subunit vaccines. These includes various virus inactivation strategies, adjuvants, nanoparticle-based vaccine delivery systems, DNA vaccines, and recombinant subunit vaccines produced using baculovirus, plant, and replication-deficient viruses as vector vaccines. Finally, future directions for the development of innovative non-infectious PRRSV vaccines are suggested. Undoubtedly there remains a need for novel PRRSV vaccine strategies targeted to deliver cross-protective, non-infectious vaccines for the control and eradication of PRRS.

A single amino acid deletion in the matrix protein of porcine reproductive and respiratory syndrome virus confers resistance to a polyclonal swine antibody with broadly neutralizing activity.

Assessment of virus neutralization (VN) activity in 176 pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV) identified one pig with broadly neutralizing activity. A Tyr-10 deletion in the matrix protein provided escape from broad neutralization without affecting homologous neutralizing activity. The role of the Tyr-10 deletion was confirmed through an infectious clone with a Tyr-10 deletion. The results demonstrate differences in the properties and specificities of VN responses elicited during PRRSV infection.