Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen.

BACKGROUNDVaccination is typically administered without regard to site of prior vaccination, but this factor may substantially affect downstream immune responses.METHODSWe assessed serological responses to initial COVID-19 vaccination in baseline seronegative adults who received second-dose boosters in the ipsilateral or contralateral arm relative to initial vaccination. We measured serum SARS-CoV-2 spike-specific Ig, receptor-binding domain-specific (RBD-specific) IgG, SARS-CoV-2 nucleocapsid-specific IgG, and neutralizing antibody titers against SARS-CoV-2.D614G (early strain) and SARS-CoV-2.B.1.1.529 (Omicron) at approximately 0.6, 8, and 14 months after boosting.RESULTSIn 947 individuals, contralateral boosting was associated with higher spike-specific serum Ig, and this effect increased over time, from a 1.1-fold to a 1.4-fold increase by 14 months (P < 0.001). A similar pattern was seen for RBD-specific IgG. Among 54 pairs matched for age, sex, and relevant time intervals, arm groups had similar antibody levels at study visit 2 (W2), but contralateral boosting resulted in significantly higher binding and neutralizing antibody titers at W3 and W4, with progressive increase over time, ranging from 1.3-fold (total Ig, P = 0.007) to 4.0-fold (pseudovirus neutralization to B.1.1.529, P < 0.001).CONCLUSIONSIn previously unexposed adults receiving an initial vaccine series with the BNT162b2 mRNA COVID-19 vaccine, contralateral boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination. This effect should be considered during arm selection in the context of multidose vaccine regimens.FUNDINGM.J. Murdock Charitable Trust, OHSU Foundation, NIH.

Evaluation of Microleakage of Stainless Steel Crowns and Pedo Jacket Crowns after Cementation With Different Luting Cements.

Aim: The present research was conducted to assess the microleakage of stainless steel crowns along with pedo jacket crowns following cementation with different luting cements. Materials and Methods: A total of 60 deciduous teeth subjected to extraction were employed in this in vitro research. These 60 specimens were randomly divided into two groups: Group I: Stainless steel crowns and Group II: Pedo Jacket crowns. Both crowns were subjected to cementation using self-cure resin-modified glass ionomer (RMGI) cement as well as by means of self-adhesive universal resin cement (RelyX luting cement). The specimens were subjected to storage in distilled water at 37°C for 24 h and were subjected to 500 thermal cycles between 5°C and 55°C using a dwell span of 30 s. Individual surfaces were assessed for the amount of dye infiltration at the boundaries by the side of the tooth-cement border beneath a stereomicroscope under 50× magnifying power. At the mesial and distal surfaces, the amount of microleakage was measured in micrometers (µm), and the mean value was computed for each sample. Results: Stainless steel crowns subject to cementation with RelyX luting cement exhibited the lowest microleakage (0.88 ± 0.78) versus self-cure RMGI cement (0.94 ± 0.78). There was no statistically significant difference found between the groups. Pedo Jacket crowns subject to cementation with RelyX luting cement exhibited the lowest microleakage (0.96. ± 0.32) while self-cure RMGI cement (1.83 ± 0.16) depicted the maximum microleakage. There was an extremely statistically noteworthy dissimilarity noted among the groups. Conclusion: The current research concluded that Pedo Jacket crowns subjected to cementation with RelyX luting cement can be regarded as an esthetically pleasing restorative alternative for numerous young patients. Applying RelyX luting cement to Pedo Jacket crowns provides a strong bolstering by composite materials that ensures the success of the therapy provided.

Campylobacter vaccination reduces diarrheal disease and infant growth stunting among rhesus macaques.

Campylobacter-associated enteric disease is estimated to be responsible for more than 160 million cases of gastroenteritis each year and is linked to growth stunting of infants living under conditions of poor sanitation and hygiene. Here, we examine naturally occurring Campylobacter-associated diarrhea among rhesus macaques as a model to determine if vaccination could reduce severe diarrheal disease and infant growth stunting. Compared to unvaccinated controls, there are no Campylobacter diarrhea-associated deaths observed among vaccinated infant macaques and all-cause diarrhea-associated infant mortality is decreased by 76% (P = 0.03). By 9 months of age, there is a 1.3 cm increase in dorsal length that equaled a significant 1.28 LAZ (Length-for-Age Z score) improvement in linear growth among vaccinated infants compared to their unvaccinated counterparts (P = 0.001). In this work, we show that Campylobacter vaccination not only reduces diarrheal disease but also potentially serves as an effective intervention that improves infant growth trajectories.

Recall responses in the lung environment are impacted by age in a pilot study of Mycobacterium bovis-BCG vaccinated rhesus macaques.

Age-related changes in the immune system increase susceptibility to infectious diseases. Vaccines are an important tool to prevent infection or boost immunological memory; however, vaccines are less effective in aged individuals. In order to protect our aging population from the threat of infectious diseases, we must gain a better understanding of age-related alterations in the immune response at the site of infection. The lung is one site of frequent infection in older individuals. In this study, we expanded on our previous work to study vaccine-induced immune responses in the local lung environment in a pilot study of aged rhesus macaques. To do this, we developed an in vivo model to probe recall responses to tuberculin challenge in the lungs 8 weeks and 16 weeks post-Mycobacterium bovis BCG vaccination by performing targeted bronchoalveolar lavages. In parallel, we determined peripheral blood responses in vaccinated animals to compare systemic and local tissue responses to tuberculin challenge. We found that following lung tuberculin challenge 8 weeks post-vaccination, aged animals had reduced T cell responses, particularly within the CD8+ T cell compartment. Aged animals had decreased CD8+ effector and memory T cell recall responses and less activated CD8+ T cells. This diminished lung CD8+ T cell response in aged animals was maintained over time. Despite changes in the CD8+ T cell compartment, lung CD4+ T cell responses were similar between age groups. In the peripheral blood, we observed age-related changes in immune cell populations and plasma levels of immune mediators that were present prior to vaccination. Lastly, we found that peripheral blood mononuclear cells from aged BCG-vaccinated animals were functional in their response to antigen stimulation, behaving in a similar manner to those from their adult counterparts. These systemic observations were similar to those found in our previous study of BCG-vaccinated baboons, supporting the notion that tissue immune responses, and not systemic responses, to vaccination and challenge are impaired with age. These findings expand on our previous work to show that in addition to the skin, age-related changes in the lung environment impact recall immune responses to vaccination and challenge. The impact of age on local tissue responses to infectious challenge should be accounted for in the development of therapeutics or medical interventions aimed at boosting immune recall responses of aged individuals.

Active Circulation of Corynebacterium ulcerans among Nonhuman Primates.

Diphtheria is rare in the United States. and many industrialized nations due to development of an effective vaccine, coupled with high vaccination coverage. Although there is continued risk of importation and transmission of Corynebacterium diphtheriae, C. ulcerans has now become the dominant source of diphtheria cases among several European countries. Bearing this in mind, a better understanding of C. ulcerans biology is clearly needed. Here, we identified active transmission of toxigenic C. ulcerans among indoor- and outdoor-housed rhesus macaques based on diphtheria toxin-specific serology assays as well as direct isolation of C. ulcerans from a recently infected animal. In addition to animal-to-animal transmission, we found serological evidence indicative of potential human transmission. Together, these results provide new details on natural Corynebacterium transmission among nonhuman primates and emphasizes the importance of maintaining high vaccination coverage to reduce the risk of potential zoonotic infection. IMPORTANCE C. ulcerans represents an emerging zoonotic agent of diphtheria, but little is known about its transmission or maintenance among animal reservoirs. In these studies, we identified diphtheria outbreaks among both outdoor- and indoor-housed rhesus macaques and isolated a toxigenic strain of C. ulcerans from a recently infected animal. Retrospective analysis indicated that toxigenic Corynebacteria have been circulating among these primates for decades with the potential for rare zoonotic transmission to humans.

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.

Evaluation of Anticaries Efficacy of Various Fluoride Varnishes on Artificial Enamel Lesion: An In Vitro Study.

AIM: Aim of the current study was to assess the anticariogenic effectiveness of different fluoride varnishes on artificially induced enamel lesions employing scanning electron microscope. MATERIALS AND METHODS: Eighty healthy, normal premolars without dental caries that were extracted in course of orthodontic therapy with all the surfaces intact were included in this study. A window, 4 × 4 mm, was made discernible on the buccal surface of each sample tooth. A demineralizing solution at 37°C was used to immerse the teeth for 48 hours to induce artificial lesions on the surface of the enamel. Following preparation of the artificial enamel lesions, the 80 premolar teeth were allocated into the four groups (20 each) depending on the fluoride varnish system used as Group I: control, Group II: Duraphat varnish, Group III: MI Varnish, and Group IV: Clinpro White Varnish. The anticariogenic effectiveness of different fluoride varnishes was evaluated employing a scanning electron microscope (SEM). RESULTS: The MI Varnish (fluoride varnish) group exhibited slightly greater (127.20 ±0.14) mean demineralized lesions, pursued by Clinpro White Varnish use (126.88 ±0.09), the control group (126.36 ±0.10) and the Duraphat varnish (124.14 ±0.08) in that order. Greater mean areas of remineralization were found with use of MI Varnish (92.40 ±0.09), pursued by the Duraphat varnish use (106.68 ±0.12), use of Clinpro White Varnish (112.36 ±0.08), and then the control group (123.08 ±0.18) in that order. Statistically significant differences were noted between the experimental groups employing the various fluoride varnishes (p <0.001). CONCLUSION: The current research concluded that the MI Varnish group presented a superior protective potential in comparison with Duraphat varnish and Clinpro White Varnish groups. CLINICAL SIGNIFICANCE: Mineral exchanges among teeth and saliva render incipient enamel lesions reversible. A 5% sodium fluoride varnish is the MI Varnish that is composed of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) to provide an excellent fluoride varnish that makes available additional bioavailable fluoride, calcium, and phosphate. Therefore, it may be fruitfully utilized in remineralization of initial carious lesions. CPP-ACP may be employed in clinical practice for drawing back or ceasing initial carious lesions. Rani KBS, Ramanna PK, Mailankote S, et al. Evaluation of Anticaries Efficacy of Various Fluoride Varnishes on Artificial Enamel Lesion: An In Vitro Study. J Contemp Dent Pract 2021;22(7):774-777.

Cellular and Humoral Immune Responses in Mice Immunized with Vaccinia Virus Expressing the SARS-CoV-2 Spike Protein.

The COVID-19 pandemic is a global health emergency, and the development of a successful vaccine will ultimately be required to prevent the continued spread and seasonal recurrence of this disease within the human population. However, very little is known about either the quality of the adaptive immune response or the viral Ag targets that will be necessary to prevent the spread of the infection. In this study, we generated recombinant Vaccinia virus expressing the full-length spike protein from SARS-CoV-2 (VacV-S) to evaluate the cellular and humoral immune response mounted against this viral Ag in mice. Both CD8+ and CD4+ T cells specific to the SARS-CoV-2 spike protein underwent robust expansion, contraction, and persisted for at least 40 d following a single immunization with VacV-S. Vaccination also caused the rapid emergence of spike-specific IgG-neutralizing Abs. Interestingly, both the cellular and humoral immune responses strongly targeted the S1 domain of spike following VacV-S immunization. Notably, immunization with VacV-expressing spike conjugated to the MHC class II invariant chain, a strategy previously reported by us and others to enhance the immunogenicity of antigenic peptides, did not promote stronger spike-specific T cell or Ab responses in vivo. Overall, these findings demonstrate that an immunization approach using VacV or attenuated versions of VacV expressing the native, full-length SARS-CoV-2 spike protein could be used for further vaccine development to prevent the spread of COVID-19.

Establishment of Monoclonal Antibody Standards for Quantitative Serological Diagnosis of SARS-CoV-2 in Low-Incidence Settings.

BACKGROUND: Serological confirmation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for understanding the dynamics of the pandemic and determining seroprevalence rates within afflicted communities. Common challenges with SARS-CoV-2 serological assays include poor analytical specificity and sensitivity and lack of a serological standard for quantitative assessment of antibody titers. METHODS: To overcome these obstacles, we developed a quantitative enzyme-linked immunosorbent assay based on an optimized 2-dimensional screening assay that utilizes SARS-CoV-2 receptor binding domain (RBD) of spike protein and SARS-CoV-2 spike S1 subunit. RESULTS: A total of 4 SARS-CoV-2-reactive monoclonal antibodies were evaluated for use as serum standards for calibrating assays performed on different days or by different laboratories. This approach provided quantitative analysis of hospitalized reverse transcription polymerase chain reaction-confirmed COVID-19 cases that in some cases reached >100 µg/mL. The assay demonstrated 72% sensitivity based on time points ranging from 2 to 52 days post-symptom onset, with 100% sensitivity at time points measured ≥13 days post-symptom onset and 100% specificity. CONCLUSIONS: Using these optimized reagents and serological standards, we believe this approach will be useful for sensitive and specific determination of seroconversion rates and quantitatively measuring the durability of antiviral antibody responses following SARS-CoV-2 infection or vaccination.

Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury.

Yellow fever (YF) is a mosquito-transmitted viral disease that causes tens of thousands of deaths each year despite the long-standing deployment of an effective vaccine. In its most severe form, YF manifests as a hemorrhagic fever that causes severe damage to visceral organs. Although coagulopathy is a defining feature of severe YF in humans, the mechanism by which it develops remains uncertain. Hepatocytes are a major target of yellow fever virus (YFV) infection, and the coagulopathy in severe YF has long been attributed to massive hepatocyte infection and destruction that results in a defect in clotting factor synthesis. However, when we analyzed blood from Brazilian patients with severe YF, we found high concentrations of plasma D-dimer, a fibrin split product, suggestive of a concurrent consumptive process. To define the relationship between coagulopathy and hepatocellular tropism, we compared infection and disease in Fah-/-, Rag2-/-, and Il2rɣ-/- mice engrafted with human hepatocytes (hFRG mice) and rhesus macaques using a highly pathogenic African YFV strain. YFV infection of macaques and hFRG mice caused substantial hepatocyte infection, liver damage, and coagulopathy as defined by virological, clinical, and pathological criteria. However, only macaques developed a consumptive coagulopathy whereas YFV-infected hFRG mice did not. Thus, infection of cell types other than hepatocytes likely contributes to the consumptive coagulopathy associated with severe YF in primates and humans. These findings expand our understanding of viral hemorrhagic disease and associated coagulopathy and suggest directions for clinical management of severe YF cases.

Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications.

Allogeneic hematopoietic stem cell transplantation (HSCT) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. Here, in a Mauritian cynomolgus macaque model of fully MHC-matched allogeneic HSCT, we report reactivations of cynomolgus polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to HSCT-associated human counterparts BK virus, Epstein-Barr virus, and human cytomegalovirus. Viral replication in recipient macaques resulted in characteristic disease manifestations observed in HSCT patients, such as polyomavirus-associated hemorrhagic cystitis and tubulointerstitial nephritis or lymphocryptovirus-associated post-transplant lymphoproliferative disorder. However, in most cases, the reconstituted immune system, alone or in combination with short-term pharmacological intervention, exerted control over viral replication, suggesting engraftment of functional donor-derived immunity. Indeed, the donor-derived reconstituted immune systems of two long-term engrafted HSCT recipient macaques responded to live attenuated yellow fever 17D vaccine (YFV 17D) indistinguishably from untransplanted controls, mounting 17D-targeted neutralizing antibody responses and clearing YFV 17D within 14 days. Together, these data demonstrate that this macaque model of allogeneic HSCT recapitulates clinical situations of opportunistic viral infections in transplant patients and provides a pre-clinical model to test novel prophylactic and therapeutic modalities.

Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus-Infected Women Despite Immune Reconstitution With Antiretroviral Therapy.

BACKGROUND: It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections. METHODS: We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24-108 years; P = .001). CONCLUSIONS: Despite antiretroviral therapy-associated improvement in CD4+ T-cell counts (nadir, <200/µL; >350/µL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.

Advanced oxidation technology for the development of a next-generation inactivated West Nile virus vaccine.

West Nile virus (WNV) is the most frequent mosquito-borne disease reported in the continental United States and although an effective veterinary vaccine exists for horses, there is still no commercial vaccine approved for human use. We have previously tested a 3% hydrogen peroxide (H2O2)-based WNV inactivation approach termed, HydroVax, in Phase I clinical trials and the vaccine was found to be safe and modestly immunogenic. Here, we describe an advanced, next-generation oxidation approach (HydroVax-II) for the development of inactivated vaccines that utilizes reduced concentrations of H2O2 in combination with copper (cupric ions, Cu2+) complexed with the antiviral compound, methisazone (MZ). Further enhancement of this oxidative approach included the addition of a low percentage of formaldehyde, a cross-linking reagent with a different mechanism of action that, together with H2O2/Cu/MZ, provides a robust two-pronged approach to virus inactivation. Together, this new approach results in rapid virus inactivation while greatly improving the maintenance of WNV-specific neutralizing epitopes mapped across the three structural domains of the WNV envelope protein. In combination with more refined manufacturing techniques, this inactivation technology resulted in vaccine-mediated WNV-specific neutralizing antibody responses that were 130-fold higher than that observed using the first generation, H2O2-only vaccine approach and provided 100% protection against lethal WNV infection. This new approach to vaccine development represents an important area for future investigation with the potential not only for improving vaccines against WNV, but other clinically relevant viruses as well.

Multiple renal calculi due to hypercalcaemia induced by over-the-counter vitamin D intoxication.

Renal stone disease is a common and painful condition. Even though it is rarely fatal, patients describe it as the worst pain in their life. While dietary calcium may decrease the risk of stone formation, patients on supplemental calcium are at higher risk. Moreover, patients with diabetes are more prone to develop renal calculi. Hypervitaminosis D is a rare cause of hypercalcaemia. This is a case of an elderly diabetic man who developed multiple calcium oxalate renal stones due to hypercalcaemia following calcium-vitamin D supplementation.

Plasma cell survival in the absence of B cell memory.

Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear. Clinical studies indicate that antigen-specific antibody responses can be maintained for many years, leading to theories that reactivation/differentiation of memory B cells into plasma cells is required to sustain long-term antibody production. Here, we present a decade-long study in which we demonstrate site-specific survival of bone marrow-derived plasma cells and durable antibody responses to multiple virus and vaccine antigens in rhesus macaques for years after sustained memory B cell depletion. Moreover, BrdU+ cells with plasma cell morphology can be detected for 10 years after vaccination/BrdU administration, indicating that plasma cells may persist for a prolonged period of time in the absence of cell division. On the basis of these results, long-lived plasma cells represent a key cell population responsible for long-term antibody production and serological memory.

Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection.

Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to lymphoid organs, virus applied to skin by scarification does not spread to draining lymph nodes. Using cutaneous infection by scarification, we analyzed the effect of viral infection on lymphatic transport and evaluated its role at the host-pathogen interface. We found that, in the absence of lymphatic vessels, canonical lymph-node-dependent immune induction was impaired, resulting in exacerbated pathology and compensatory, systemic priming. Furthermore, lymphatic vessels decouple fluid and cellular transport in an interferon-dependent manner, leading to viral sequestration while maintaining dendritic cell transport for immune induction. In conclusion, we found that lymphatic vessels balance immune activation and viral dissemination and act as an "innate-like" component of tissue host viral defense.

Tobacco Abuse and Associated Oral Lesions among Interstate Migrant Construction Workers.

AIM: The present study was conducted to assess the prevalence of tobacco use and associated oral mucosal lesions among construction workers of Cochin, Kerala, India. MATERIALS AND METHODS: A cross-sectional study was carried at various construction sites of Cochin and 2,163 workers were selected using multistage sampling method and were interviewed and examined. Information regarding demographic details, form, type, frequency of tobacco use, earlier attempt to quit, and willingness to quit tobacco use was obtained using predesigned questionnaire. The oral health status was recorded on the World Health Organization oral health assessment form 1997, and the examination was carried out under natural light using mouth mirrors and probe. Data thus collected were analyzed using Statistical Package for the Social Sciences version 17 (Chicago, Illinois, USA) statistical software package. Chi-square test was applied. RESULTS: Among the 2,163 workers, 1,952 were tobacco users and 211 were nonusers. Among the users, 1,021 use smokeless form, 372 use smoked form, and 559 use both. Premalignant lesions/conditions were more commonly seen with tobacco habit, with leukoplakia (14.75%) being the most common followed by oral submucous fibrosis in 201 (9.3%), candidiasis in 123 (5.7%), ulceration in 131 (6.05%), abscess in 59 (2.73%), smokers palate in 58 (2.68%), lichen planus in 21 (0.97%), and malignant tumor in 2 (0.1%). CONCLUSION: Commonness of abusive habits and oral premalig-nant lesions or conditions was considerable among the workers. Control and early diagnosis through workplace screening are the major backbones for the control of oral cancer. CLINICAL SIGNIFICANCE: Building workers are unprotected from various health hazards at workplace. Lack of access to health services makes the situation unsatisfactory. Poor literacy and low socioeconomic status have resulted in practice of tobacco, smoking, and chewing in the majority of them. Hence, it is our responsibility to find and guide them with a proper oral health education.

Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine.

West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2-8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate.

Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis.

BACKGROUND: Many adult immunization schedules recommend that tetanus and diphtheria vaccination be performed every 10 years. In light of current epidemiological trends of disease incidence and rates of vaccine-associated adverse events, the 10-year revaccination schedule has come into question. METHODS: We performed cross-sectional analysis of serum antibody titers in 546 adult subjects stratified by age or sex. All serological results were converted to international units after calibration with international serum standards. RESULTS: Approximately 97% of the population was seropositive to tetanus and diphtheria as defined by a protective serum antibody titer of ≥0.01 IU/mL. Mean antibody titers were 3.6 and 0.35 IU/mL against tetanus and diphtheria, respectively. Antibody responses to tetanus declined with an estimated half-life of 14 years (95% confidence interval, 11-17 years), whereas antibody responses to diphtheria were more long-lived and declined with an estimated half-life of 27 years (18-51 years). Mathematical models combining antibody magnitude and duration predict that 95% of the population will remain protected against tetanus and diphtheria for ≥30 years without requiring further booster vaccination. CONCLUSIONS: These studies demonstrate that durable levels of protective antitoxin immunity exist in the majority of vaccinated individuals. Together, this suggests that it may no longer be necessary to administer booster vaccinations every 10 years and that the current adult vaccination schedule for tetanus and diphtheria should be revisited.

Comprehensive maternal serum proteomic profiles of preclinical and clinical preeclampsia.

We systematically characterized maternal serum proteome in women with clinical preeclampsia (PE) and asymptomatic women in early pregnancy that subsequently developed PE. Clinical PE cohort comprised 30 patients with mild PE, 30 with severe PE, and 58 normotensive women. Preclinical PE cohort included 149 women whose serum samples were collected at 8-14 gestational weeks and in whom 30 women later developed mild and 40 severe PE. Serum proteome was analyzed and enzyme-linked immunosorbent assays were used for protein quantification. In Clinical PE, fibronectin, pappalysin-2, choriogonadotropin-beta, apolipoprotein C-III, cystatin-C, vascular endothelial growth factor receptor-1, and endoglin were more abundant compared to normotensive women. In preclinical PE, differently expressed proteins included placental, vascular, transport, matrix, and acute phase proteins. Angiogenic and antiangiogenic proteins were not significant. We conclude that placental and antiangiogenic proteins are abundant in clinical PE. In preclinical PE, proteomic profile is distinct and different from that in clinical PE.