High Levels Of IgG Antibodies Research Articles

Antibody Response to the SARS-CoV-2 Spike and Nucleocapsid Proteins in Patients with Different COVID-19 Clinical Profiles.

The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19.

A multivalent Plasmodium falciparum circumsporozoite protein-based nanoparticle malaria vaccine elicits a robust and durable antibody response against the junctional epitope and the major repeats.

Plasmodium falciparum (Pf) malaria continues to cause considerable morbidity and mortality worldwide. The circumsporozoite protein (CSP) is a particularly attractive candidate for designing vaccines that target sporozoites-the first vertebrate stage in a malaria infection. Current PfCSP-based vaccines, however, do not include epitopes that have recently been shown to be the target of potent neutralizing antibodies. We report the design of a SpyCatcher-mi3-nanoparticle-based vaccine presenting multiple copies of a chimeric PfCSP (cPfCSP) antigen that incorporates these important "T1/junctional" epitopes as well as a reduced number of (NANP)n repeats. cPfCSP-SpyCatcher-mi3 was immunogenic in mice eliciting high and durable IgG antibody levels as well as a balanced antibody response against the T1/junctional region and the (NANP)n repeats. Notably, the antibody concentration elicited by immunization was significantly greater than the reported protective threshold defined in a murine challenge model. Refocusing the immune response toward functionally relevant subdominant epitopes to induce a more balanced and durable immune response may enable the design of a more effective second generation PfCSP-based vaccine.

An Adjuvanted Inactivated SARS-CoV-2 Microparticulate Vaccine Delivered Using Microneedles Induces a Robust Immune Response in Vaccinated Mice.

SARS-CoV-2, the causal agent of COVID-19, is a contagious respiratory virus that frequently mutates, giving rise to variant strains and leading to reduced vaccine efficacy against the variants. Frequent vaccination against the emerging variants may be necessary; thus, an efficient vaccination system is needed. A microneedle (MN) vaccine delivery system is non-invasive, patient-friendly, and can be self-administered. Here, we tested the immune response produced by an adjuvanted inactivated SARS-CoV-2 microparticulate vaccine administered via the transdermal route using a dissolving MN. The inactivated SARS-CoV-2 vaccine antigen and adjuvants (Alhydrogel® and AddaVax™) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer matrices. The resulting MP were approximately 910 nm in size, with a high percentage yield and percent encapsulation efficiency of 90.4%. In vitro, the vaccine MP was non-cytotoxic and increased the immunostimulatory activity measured as nitric oxide release from dendritic cells. The adjuvant MP potentiated the immune response of the vaccine MP in vitro. In vivo, the adjuvanted SARS-CoV-2 MP vaccine induced high levels of IgM, IgG, IgA, IgG1, and IgG2a antibodies and CD4+ and CD8+ T-cell responses in immunized mice. In conclusion, the adjuvanted inactivated SARS-CoV-2 MP vaccine delivered using MN induced a robust immune response in vaccinated mice.

An oral NoV-rAd5 vaccine with built-in dsRNA adjuvant elicits systemic immune responses in mice

Norovirus (NoV) is an enteric pathogen notorious for causing epidemics of acute gastroenteritis. An effective vaccine against NoV is therefore urgently needed. A short double-stranded RNA (dsRNA) has been described that acts as a retinoic-acid-inducible gene-I agonist to induce the production of type I interferon; it also exhibits adjuvant activity. Using built-in dsRNA of different lengths (DS1 and DS2), we developed a recombinant adenovirus 5 (rAd5) expressing NoV VP1, and evaluated its immunogenicity following oral administration in a mouse model. An in vitro study demonstrated that the dsRNA adjuvants significantly enhanced VP1 protein expression in infected cells. The oral administration of both rAd5-VP1-DS vaccines elicited high serum levels of VP1-specific IgG and blocking antibodies, as well as strong and long-lasting mucosal immunity. There was no apparent difference in immunostimulatory effects in immunised mice between the two dsRNA adjuvants. This study indicates that an oral NoV-rAd5 vaccine with a built-in dsRNA adjuvant may be developed to prevent NoV infection in humans.

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

High levels of antibodies 6 months after COVID-19 vaccination in children with severe chronic diseases: A prospective longitudinal case series.

The Immunogenicity of a VLP-based Malaria Vaccine Targeting CSP in Pregnant and Neonatal Mice.

Maternal antibodies are passively transferred to the fetus via the placenta during gestation and can play an important role in protecting the newborn from infection. For example, in malaria-endemic regions, maternal antibodies likely provide substantial protection against Plasmodium falciparum malaria in the first 6 months of life. However, circulating maternal antibodies can also interfere with vaccine efficacy. Here, we used a mouse maternal transfer model to evaluate whether maternal antibodies interfere with the responsiveness to a virus-like particle (VLP)-based vaccine targeting the CIS43 epitope of the malaria circumsporozoite protein (CSP). We found immunized dams passively transfer to pups high levels of anti-CSP IgG antibodies that steadily decline as the animals age. We also found that the neonatal offspring of immunized mice do not respond to de novo immunization with the CIS43-targeted VLP vaccine until maternal antibody titers decline below an inhibitory threshold. These findings may have important implications for delineating the delicate balance between protection conferred by maternal antibodies and the offspring's ability to respond to immunization.

Avascular Necrosis of HIP After Active Covid-19 Infection

AbstractBackground and objectives: The exact course of SARS -2(COVID-19) and its complications on multiorgan systemare complex and still under studies. Musculoskeletal system has also been affected post covid in various forms.This study was taken up to analyse the effects of covid-19 disease on the hip bone and join tissue.Materials and Methods: Retrospective analysis of ten patients was done who had been hospitalised with covid-19infection and later complained of hip pain. They underwent MR imaging and were found to have degenerativechanges characterizing with avascular necrosis (AVN) of head of femur .One of them had history of previoussurgery of femur with PFN, doin well but developed AVN after covid.Results: Observation of this group showed a clear correlation among the history of COVID-19 disease in thepatients, moderately severe symptoms, high levels of IgG antibodies, and the time of occurrence of joint changes.No other risk factors for AVN or auto-immune or degenerative diseases were found in the study group. The groupof patients responded well to empirical treatment with anti-inflammatory drugs ans supportive therapy, whichsubsided acute inflammatory symptoms and pain in the joints.Conclusions: It is concluded that there have been obvious musculoskeletal complications in covid patientsincluding AVN which could be attributed to the high use steroids and microembolism leading to bone necrosis.Hence more studies and long follow-up is suggested.

Evaluation of porcine circovirus type 2 double vaccination in weaning piglets that reared for gilts under field conditions.

The objective of the present study was to evaluate the efficacy of a porcine circovirus type 2 (PCV2) double vaccination in weaning piglets reared for gilts under field conditions. The study was conducted at a Greek farrow-to-finish conventional pig farm with a previous history of PCV2 infections. The trial included 96 female piglets at 21 days of age, which were equally allocated to two different study groups. Piglets of the group-1 received a single PCV2 vaccination at 21 days of age, while piglets of the group-2 were double vaccinated against PCV2, at 21 and 42 days of age. The results indicated that the piglets of group-2 had better growth performance, as they showed higher body weight (BW) and average daily weight gain (ADWG). In addition, ELISA tests showed that the double- vaccinated piglets presented a better humoral response against PCV2, as higher levels of IgG antibodies were detected in them than the piglets of the group-1. In conclusion, the current results suggested that a double PCV2 vaccination of piglets, reared for gilts, on a PCV2-affected farm could lead to higher protection against the virus.

Immunogenicity and safety of a two-dose regimen with hepatitis E virus vaccine in healthy adults in rural Bangladesh: A randomized, double-blind, controlled, phase 2/pilot trial

BackgroundHepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide and it contributes to considerable maternal and neonatal mortality and morbidity in many low-income countries like Bangladesh. A three-dose regimen of a vaccine against HEV (HEV 239) has shown promising results in China. The effects and safety of this vaccine in other populations and with different dosing regimens remains uncertain. ObjectivesInvestigate the immune response and safety of a two-dose regimen with the HEV 239 vaccine among healthy adults. Examine the feasibility of conducting a larger HEV 239 vaccine trial in rural Bangladesh. MethodsOne-hundred healthy men and non-pregnant women 16–39 years old were randomized in a 1:1 ratio to receive two doses of either the study (HEV) or control (Hepatitis B virus, HBV) vaccine (at 0, 1 month). Blood samples were collected at day 0, day 60 and 2 years after vaccination. The primary endpoints were the proportion and severity of adverse events up to 2 months after dose one and the longitudinal shift in anti-HEV IgG levels from day 0 to day 60 and 2 years after vaccination. ResultsAdverse events to HEV 239 were comparable to the control vaccine, mild in severity and resolved within one to nine days. All participants in the study group seroconverted and achieved high levels of HEV IgG antibodies that remained positive for two years in all but one. A T-cell response was detected one month after HEV 239 vaccination. ConclusionOur results show that two doses of the HEV 239 vaccine produces broad and likely functional immune responses against HEV that remain for at least two years. The safety profile was acceptable and a phase four study of HEV 239 in rural Bangladesh is feasible.ClinicalTrials.gov Identifier: NCT02759991.

Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-β, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-β, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy.

Comparative analysis of the effectiveness of vaccines against SARS-CoV-2 3 months after revaccination

Since 2021, Turkmenistan has been vaccinating the population against COVID-19. The aim of the work is a comparative analisis of the effectiveness of vaccines against SARS–CoV-2 used in mass vaccination of the population in the development of population immunity.Research materials. The blood serum of 960 people vaccinated with “Sputnik-lite” or “BIOvac” was used in the work.Conclusion. 3 months after revaccination, 100 % of vaccinated patients have a high level of specific IgG antibodies in their blood serum. A comparative analysis of the effectiveness of two vaccines “Sputnik-lite” and “BIOvac”, showed that a longer immune response persists after the introduction of the vaccine “Sputnik-lite”.

Combined monitoring of IgG and IgA anti-Spike and anti-Receptor binding domain long term responses following BNT162b2 mRNA vaccination in Greek healthcare workers.

Studies on the humoral response to homologous BNT162b2 mRNA-vaccination focus mainly on IgG antibody dynamics, while long-term IgA kinetics are understudied. Herein, kinetics of IgG and IgA levels against trimeric-Spike (S) and Receptor-Binding-Domain (RBD) were evaluated by in-house ELISAs in 146 two-dose vaccinated Greek healthcare workers (HCWs) in a 9-month period at six time points (up to 270 days after the first dose). The effect of a homologous booster third dose was also studied and evaluated. The peak of immune response was observed 21 days after the second dose; 100% seroconversion rate for anti-S and anti-RBD IgG, and 99.7% and 96.3% respectively for IgA. IgG antibody levels displayed higher increase compared to IgA. Declining but persistent anti-SARS-CoV-2 antibody levels were detected 9 months after vaccination; IgG and IgA anti-S levels approached those after the first dose, while a more rapid reduction rate for anti-RBD antibodies led to significantly lower levels for both classes, supporting the need for a booster dose. Indeed, a homologous booster third dose resulted in enhanced levels of anti-S of both classes, whereas anti-RBD didn't exceed the peak levels after the second dose. Previous SARS-CoV-2 infection, flu vaccination, BMI<35 and the occurrence of an adverse event upon vaccination, were associated with higher IgG antibody levels over time, which however were negatively affected by age increase and the presence of chronic diseases. Overall, after concurrently using the S and RBD target-antigens in in-house ELISAs, we report in addition to IgG, long-term persistence of IgA antibodies. Regarding antibody levels, homologous mRNA vaccination gives rise to an effective anti-viral protection up to 9 months negatively correlated to age. Considering that COVID-19 is still a matter of public concern, booster vaccine doses remain critical to vulnerable individuals.

Nanoparticle-Based Bivalent Swine Influenza Virus Vaccine Induces Enhanced Immunity and Effective Protection against Drifted H1N1 and H3N2 Viruses in Mice.

Swine influenza virus (SIV) circulates worldwide, posing substantial economic loss and disease burden to humans and animals. Vaccination remains the most effective way to prevent SIV infection and transmission. In this study, we evaluated the protective efficacy of a recombinant, baculovirus-insect cell system-expressed bivalent nanoparticle SIV vaccine in mice challenged with drifted swine influenza H1N1 and H3N2 viruses. After a prime-boost immunization, the bivalent nanoparticle vaccine (BNV) induced high levels of hemagglutination inhibition (HAI) antibodies, virus-neutralization (VN) antibodies, and antigen-specific IgG antibodies in mice, as well as more efficient cytokine levels. The MF59 and CPG1 adjuvant could significantly promote both humoral and cellular immunity of BNV. The MF59 adjuvant showed a balanced Th1/Th2 immune response, and the CPG1 adjuvant tended to show a Th1-favored response. The BALB/c challenge test showed that BNV could significantly reduce lung viral loads and feces viral shedding, and showed fewer lung pathological lesions than those in PBS and inactivated vaccine groups. These results suggest that this novel bivalent nanoparticle swine influenza vaccine can be used as an efficacious vaccine candidate to induce robust immunity and provide broad protection against drifted subtypes in mice. Immune efficacy in pigs needs to be further evaluated.

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT.

Our previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear. In this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine. MP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ+ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group. MP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.

Outliers Matter-Correlation between S1 IgG SARS-CoV-2 Antibodies and Neutralizing SARS-CoV-2 Antibodies.

Vaccination against the SARS-CoV-2 virus or infection with SARS-CoV-2 will lead to the development of IgG antibodies against the S1 protein of the SARS-CoV-2 virus. However, even despite having high levels of IgG antibodies against the S1 protein of the SARS-CoV-2 virus, (re-)infection may occur. We thus examined 2994 consecutive blood samples of outpatients from the Berlin-Brandenburg area in Germany in which IgG antibodies against the S1 protein of the SARS-CoV-2 virus as well as neutralizing SARS-CoV-2 virus antibodies were determined from the same sample. When analyzing the entire study population (2994 outpatients), we saw that S1 IgG antibodies (women: 223.98 ± 3.81; men: 207.80 ± 4.59; p = 0.014) and neutralizing antibodies (women: 66.65 ± 0.82; men: 62.88 ± 1.01; p = 0.021) are slightly higher in women than in men. Curve fitting revealed a good non-linear relationship between S1 IgG and neutralizing SARS-CoV-2 antibodies. However, 51 out of the 2994 blood samples from individual subjects were positive with regard to the neutralizing antibodies and at the same time negative for S1 IgG antibodies, and 112 out of the 2994 blood samples from individual subjects were negative with regard to the neutralizing antibodies and at the same time positive for S1 IgG antibodies. In conclusion, our study shows that there is a relevant number of patients who, despite developing significant titers of S1 antibodies, do not have relevant amounts of neutralizing antibody titers and are probably at high risk of (re-)infection.

Features of the Humoral Response to Infection, Vaccination, and Revaccination during COVID-19.

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.

Occurrence of Seropositivity of Toxoplasma gondii, Cytomegalovirus, and Rubella Infections in Pregnant Women

Aim: To assess the seropositivity for Toxoplasma gondii, Rubella virus, and Cytomegalovirus among pregnant females in Hyderabad, Sindh, Pakistan Methodology: A prospective study was undertaken at the Department of Gynecology and Obstetrics, Bahria University of Health Sciences, Karachi, Pakistan between March 2020 to June 2021. All women with confirmed pregnancies were eligible to participate in the study. Women with ectopic pregnancy or women who were not receiving prenatal care at our center were excluded. All participants underwent assessment for antibody Titres for Toxoplasmosis, Rubella, and CMV. Blood specimens of participating women were obtained in aseptic conditions for laboratory investigations. The IgM and IgG antibodies for Toxoplasma gondii, Rubella, and CMV along with IgG antibodies for CMV and Toxoplasma gondii were assessed comprehensively. Seropositivity was stratified with respect to age groups. Results: A total of 336 women with a mean age of 26.88 ± 3.77 years were included. The rate of seropositivity for anti-Toxoplasma IgM, anti-Rubella IgM, and anti-CMV IgM was 1.2%, 0.6%, and 2.7%, consecutively. A total of four (1.2%) cases were positive for anti-Toxoplasma IgM. 126(37.5%) women were positive for Anti-Toxoplasma IgG. For the three positive cases of both IgM and IgG, avidity test showed high avidity. Overall, one case for toxoplasma gondii was detected. Two women were positive for anti-Rubella IgM only (positive cases). Overall, 291 (86.6%) individuals were positive for Rubella IgG. Overall, two cases of Rubella were detected in our study. All nine positive cases of anti-CMV IgM antibodies were also positive for anti-CMV IgG. For these nine cases, anti-CMV IgG avidity was reported which turned out to be intermediary or high. Overall, we did not detect a case of CMV in our study. Conclusion: We found high levels of IgG antibodies for Rubella and CMV, indicating past infection/immunity. The present study highlighted the seroprevalence rate of Toxoplasma gondii, CMV, and Rubella in a cohort of pregnant women from Sindh. However, this rate could be under-reported as many women do not avail of antenatal services during pregnancy, especially from rural Sindh, Pakistan. Nevertheless, this study adds to the current literature. Furthermore, it is recommended to regularly screen pregnant females for these infections. Keywords: Cytomegalovirus, rubella, seroprevalence, torch infections, toxoplasma gondii

Towards the development of an epitope-focused vaccine for SARS-CoV-2

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions.Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Sublingual immunisation with GBS serotype III capsular polysaccharide-tetanus toxoid conjugate vaccine induces systemic and mucosal antibody responses which are opsonophagocytic and inhibit GBS colonisation of vaginal epithelial cells

No vaccines are currently licensed against Group B streptococcus (GBS), an important cause of morbidity and mortality in babies and adults. Using a mouse model, and in vitro opsonophagocytosis and colonisation assays, we evaluated the potential of a sublingually-administered polysaccharide-conjugate vaccine against GBS serotype III. Sublingual immunisation of mice with 10 µg of GBS conjugate vaccine once a week for 5 weeks induced a substantial systemic IgG anti-polysaccharide response which was similar to the level induced by subcutaneous immunsation. In addition, sublingual immunisation also induced mucosal (IgA) antibody responses in the mouth, intestines and vagina. Immune sera and intestinal washes were functionally active at mediating killing of the homologous GBS serotype III in an opsonophagocytosis assay. In addition, intestinal and vaginal washes inhibited the colonisation of mouse vaginal epithelial cells by the vaccine homologous strain. These results suggest that, in addition to the induction of high levels of IgG antibodies that could be transduced from the immunised mother to the foetus to protect the newborn against GBS infection, sublingual immunisation can elicit a substantial mucosal antibody response which might play an important role in the prevention of GBS colonisation in immunised women, thereby eliminating the risk of GBS transmission from the mother to the baby during pregnancy or at birth.

Enhanced Immunogenicity of an Influenza Ectodomain Matrix-2 Protein Virus-like Particle (M2e VLP) Using Polymeric Microparticles for Vaccine Delivery.

In this study, we demonstrate how encapsulating a conserved influenza ectodomain matrix-2 protein virus-like particle (M2e5x VLP) into a pre-crosslinked bovine serum albumin (BSA) polymeric matrix enhances in vitro antigen immunogenicity and in vivo efficacy. The spray-dried M2e5x VLP-loaded BSA microparticles (MPs) showed enhanced stimulation of antigen presenting cells (APCs), as confirmed through nitrite production and increased antigen–cell interactions seen in real time using live-cell imaging. Next, to further boost the immunogenicity of M2e5x VLP microparticles, M2e5x MPs were combined with Alhydrogel® and monophosphoryl lipid-A (MPL-A®) adjuvant microparticles. M2e5x VLP MPs and the combination VLP M2e5x VLP + Alhydrogel® + MPL-A® MPs elicited a significant increase in the expression of antigen-presenting molecules in dendritic cells compared to M2e5x VLP alone. Lastly, for preliminary evaluation of in vivo efficacy, the vaccine was administered in mice through the skin using an ablative laser. The M2e5x VLP + Alhydrogel® + MPL-A® MPs were shown to induce high levels of M2e-specific IgG antibodies. Further, a challenge with live influenza revealed heightened T-cell stimulation in immune organs of mice immunized with M2e5x VLP + Alhydrogel® + MPL-A® MPs. Hence, we utilized the advantages of both VLP and polymeric delivery platforms to enhance antigen immunogenicity and adaptive immunity in vivo.