Successful Immunization Research Articles

Antiviral Potential of Selected Medicinal Herbs and Their Isolated Natural Products

Viruses are responsible for a variety of human pathogenesis. Owing to the enhancement of the world population, global travel, and rapid urbanization, and infectious outbreaks, a critical threat has been generated to public health, as preventive vaccines and antiviral therapy are not available. Herbal medicines and refined natural products have resources for the development of novel antiviral drugs. These natural agents have shed light on preventive vaccine development and antiviral therapies. This review intends to discuss the antiviral activities of plant extracts and some isolated plant natural products based on mainly preclinical (in vitro and in vivo) studies. Twenty medicinal herbs were selected for the discussion, and those are commonly recognized antiviral medicinal plants in Ayurveda (Zingiber officinale, Caesalpinia bonducella, Allium sativum, Glycyrrhiza glabra, Ferula assafoetida, Gymnema sylvestre, Gossypium herbaceum, Phyllanthus niruri, Trachyspermum ammi, Withania somnifera, Andrographis paniculata, Centella asiatica, Curcuma longa, Woodfordia fruticose, Phyllanthus emblica, Terminalia chebula, Tamarindus indica, Terminalia arjuna, Azadirachta indica, and Ficus religiosa). However, many viruses remain without successful immunization and only a few antiviral drugs have been approved for clinical use. Hence, the development of novel antiviral drugs is much significant and natural products are excellent sources for such drug developments. In this review, we summarize the antiviral actions of selected plant extracts and some isolated natural products of the medicinal herbs.

T cell activation niches-Optimizing T cell effector function in inflamed and infected tissues.

Successful immunity to infection, malignancy, and tissue damage requires the coordinated recruitment of numerous immune cell subsets to target tissues. Once within the target tissue, effector T cells rely on local chemotactic cues and structural cues from the tissue matrix to navigate the tissue, interact with antigen-presenting cells, and release effector cytokines. This highly dynamic process has been "caught on camera" in situ by intravital multiphoton imaging. Initial studies revealed a surprising randomness to the pattern of T cell migration through inflamed tissues, behavior thought to facilitate chance encounters with rare antigen-bearing cells. Subsequent tissue-wide visualization has uncovered a high degree of spatial preference when it comes to T cell activation. Here, we discuss the basic tenants of a successful effector T cell activation niche, taking cues from the dynamics of Tfh positioning in the lymph node germinal center. In peripheral tissues, steady-state microanatomical organization may direct the location of "pop-up" de novo activation niches, often observed as perivascular clusters, that support early effector T cell activation. These perivascular activation niches appear to be regulated by site-specific chemokines that coordinate the recruitment of dendritic cells and other innate cells for local T cell activation, survival, and optimized effector function.

Effective immunization scenarios by vaccination against COVID-19 obtained through Bayesian analysis

The COVID-19 pandemic caused a health crisis on an unprecedented scale, due to the unstoppable spread of the disease through the global integration provided by the current strongly globalized society. Isolation policies recommended by WHO impacted countries economies, making it necessary to implement a range of economic, health, social and economic security policies, such as: financial aid packages for the population and companies, investment of resources for the structuring of hospital beds for the treatment of patients, implementation of population testing programs, among others. The impact of the pandemic proved to be quite significant especially for the so-called "developing countries", due to the difficulties in establishing the aforementioned range of security policies as well as mass testing of the population in order to reliably map the disease spreading. The implementation of those measure were limited not only by economic reasons, but also by political impediments. In the present study, a Bayesian analysis of the immunization rate against COVID-19 through vaccination, evaluating the immunization scenarios lasting or temporary. The logistics required for the vaccination campaign in Brazil were assessed by considering uncertainties in determining the daily rate of immunization, as well as the effectiveness of the vaccine made available for the population. In this intent, an epidemiological model was used compartmentalized, calibrated against historical data using the CATMIP stochastic algorithm. The obtained results indicate that the daily vaccination rate is the most important parameter of a successful immunization program, given an effectiveness rate equal or superior to 50%. However, a massive immunization rate needs to be conjugated with a responsible relaxing of the social distancing measures after the vaccination program start, under the risk of compromising any positive result in terms of the number of contaminated and deceased individuals.

Pakistan Ranks Third Globally With the Most Unvaccinated Children: Is the Impact of Parental Perception and Attitude on Immunization an Essential Contributing Factor to an Unsuccessful Vaccination Coverage?

IntroductionHaving the third-highest burden of child mortality and ranking third globally for the most under-vaccinated children, Pakistan contains 15% of its population under the age of five, which accounts for 50% of the mortality rate in this country. Every year, almost three million children miss out on an entire course of the most readily available vaccines, leaving them vulnerable to life-threatening diseases. The Expanded Program of Immunization (EPI) was launched in 1978 to protect children from vaccine-preventable childhood diseases. It is the main program through which routine immunization is provided to the public. However, since its inception within Pakistan, it has encountered many problems, including a lack of parental awareness and education. Low literacy rate, socio-economic disparities, cultural and religious beliefs have made parents doubtful about vaccinations. This term is known as vaccine hesitancy. Belief in conspiracy theories has also led to reduced vaccination coverage in Pakistan.Methods A cross-sectional study was conducted on 300 parents with children under five, chosen from Karachi, Pakistan, through a convenience sampling technique. The data was collected via 300 self-administered or researcher administered questionnaires. Associations were evaluated using the chi-square test with the level of significance taken as p < 0.05 and Cramer's V to determine the strength of these associations. Data analysis was done using Statistical Package for the Social Sciences (SPSS) version 20.0. Results Strong associations were found between parental knowledge of immunization, vaccines, and willingness to get their children immunized. Associations were greater and significant in parents with a higher level of education compared to lower. However, lack of knowledge about certain essential vaccines like Pentavalent, Pneumococcal, and IPV was an important aspect to consider. Also, it was noted that their inability to access these free vaccines was due to their own firm beliefs. It was also about the lack of awareness and facilities for a better and beneficial program. 22.3% of parents said that administering multiple vaccines at a time would be harmful to their child, and 21.7% believed it would cause the disease it's supposed to prevent. However, the majority of the parents said they would strongly recommend others to get vaccinated. In this study, religions included and investigated mostly encouraged vaccination to their relatives (p value= 0.079). Occupation and Monthly income had little to no effect on the immunization regime of young children. ConclusionAn impact of higher levels of education on the perceptions and attitudes of parents regarding the immunization of children was noted. Consequently, as religion, gender, occupation, and monthly income do not affect parents' perceptions regarding immunizations, the problem lies within their knowledge and understanding of basic medical science and easily communicable diseases. Oblivious to the consequences of contracting a lethal disease, it has developed a laid-back attitude amongst parents. Hence, awareness and education of parents regarding vaccine-preventable diseases by the healthcare system and the governing bodies can lead to a higher successful immunization rate.

A Community-Based Management of COVID-19 in a Mobile Container Unit.

Vaccine uptake is a multifactor measure of successful immunization outcomes that includes access to healthcare and vaccine hesitancy for both healthcare workers and communities. The present coronavirus disease (COVID-19) pandemic has highlighted the need for novel strategies to expand vaccine coverage in underserved regions. Mobile clinics hold the promise of ameliorating such inequities, although there is a paucity of studies that validate environmental infection in such facilities. Here, we describe community-based management of COVID-19 through a Smart Pod mobile clinic deployed in an underserved community area in the United States (Aldine, Harris County, TX, USA). In particular, we validate infection control and biological decontamination of the Smart Pod by testing surfaces and the air-filtration system for the COVID-19 virus and bacterial pathogens. We show the Smart Pod to be efficacious in providing a safe clinical environment for vaccine delivery. Moreover, in the Smart Pod, up-to-date education of community healthcare workers was provided to reduce vaccine hesitancy and improve COVID-19 vaccine uptake. The proposed solution has the potential to augment existing hospital capacity and combat the COVID-19 pandemic locally and globally.

Role of hepatitis A virus in diabetes mellitus.

BACKGROUNDAlthough much information is available regarding hepatitis C virus infection and diabetes, less is known about the relationship between hepatitis A virus (HAV) infection and diabetes. AIMTo examine the roles of HAV in diabetes risk.METHODSThis cross-sectional study population included data from the National Health and Nutrition Examination Survey collected between 2005-2012. Adult subjects (≥ 20 years old) with available body mass index measurements, defined diabetes status, history of HAV vaccination, and HAV serology were included. HAV vaccination was based on self-reported history. Successful HAV immunization was defined as the presence of both vaccination and anti-HAV antibody. HAV infection was defined by the absence of vaccination but presence of anti-hepatitis A antibody. The odds ratio (OR) for diabetes with 95% confidence intervals (95%CI) was calculated for each HAV status and then adjusted for covariates. Sensitivity tests, based on different definitions of diabetes, were performed to verify the results. RESULTSAmong 19942 subjects, 4229 subjects (21.21%) received HAV vaccination and HAV antibody was present in 9224 subjects (46.25%). Although HAV infection was associated with an increased risk of diabetes (OR: 1.13; 95%CI: 1.08-1.18), HAV vaccination was not associated with diabetes (OR: 1.06; 95%CI: 0.95-1.18), and successful HAV immunization had no impact on the risk of diabetes (OR: 1.11; 95%CI: 0.97-1.27). Thus, HAV infection was an unlikely cause of diabetes. Alternatively, in non-vaccinated subjects, diabetes increased the risk of HAV infection by 40% (OR: 1.40, 95%CI: 1.27-1.54). CONCLUSIONAn association between HAV infection and diabetes is observed which is best explained by an increased risk of HAV infection in diabetic patients. Diabetic subjects are more susceptible to HAV. Thus, HAV vaccination is highly recommended in diabetic patients.

Vaccine Hesitancy: Past and Present in the COVID-19 Era

Vaccine-hesitant individuals are a heterogeneous group that are indecisive in varying degrees – more of a spectrum – about specific vaccines or vaccination in general. Vaccine hesitancy is complex, varying by vaccine, time, context, geographic region, and sub-population. There is an “infodemic” that needs to be fought alongside the pandemic as exposure to misinformation is linked to a reduction in an individual’s intentions to vaccinate. In addressing vaccine hesitancy, it is key to 1) identify the subpopulations susceptible to vaccine hesitancy, 2) diagnose issues through various research methods – surveys, in-depth interviews, focus groups, or media monitoring – and 3) develop context-tailored, evidence-based interventions to address those reasons. Sensitivity to the context and effective communication are key to successful immunization programs, alongside other critical factors (confidence, complacency and convenience – the 3Cs model); engaging stakeholders in dialogue is critical to intervention design and implementation.

Suppression of Extracellular Vesicle CD47 Induces Systemic Anti-DLBCL Immunity

Purpose:Tumor cells evade the immune surveillance by up-regulating surface expression of CD47, which interacts with SIRPa on macrophages to elicit the immune checkpoint response. Anti-CD47 antibody (IBI188) has shown promise in treating tumors, including Diffuse large B cell lymphoma (DLBCL). The objective response rate among DLBCL was 73% (ClinicalTrials.gov number, NCT02953509.). The basis of differential therapeutic success between patients remains unknown. Extracellular vesicles (EVs) carry bioactive molecules that influence the immune system. CD47 has be found on surface of EVs. The purpose of this study is to explore whether EV CD47 contributes to immunosuppression and is associated with anti-CD47 response in DLBCL.Methods: 1.Kaplan-Meier curves and Cox regression models were used to analyze PFS and OS. The area under the ROC curve (AUC) was used to assess the predicted validity of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) model and the NCCN-IPI+ CD47 model.2.Immunofluorescence experiment was used to detect the infiltration of M1 and M2 subtype macrophages in DLBCL tumor tissue. M1 and M2 macrophages were generated from peripheral blood mononuclear cells obtained from healthy donors. Immunoelectron microscopy, flow cytometry and western blot were performed to detect CD47 on the surface of the EVs derived from DLBCL cells. The activity of macrophage phagocytosis of DLBCL cells was detected by confocal-based phagocytosis assay and flow cytometry-based phagocytosis assay.3.In DLBCL xenografts, the IBI188 antibody was a macrophage immune checkpoint inhibitor blocking CD47 that induces tumor-cell phagocytosis.4.Peripheral blood mononuclear cells from DLBCL patients and healthy donors was collected for EVs purification and subsequent detection of human CD47 proteins by ELISA.Results 1.The elevated expression of CD47 in DLBCL is significantly correlated with poor PFS and OS in a univariate analysis, and is statistically significant after adjusting for the NCCN-IPI in the univariate and multivariate analysis (Figure 1A, B). AUC analysis with cross-validation showed that the combination of the CD47 signature and NCCN-IPI had a better prediction of PFS and OS than without the CD47 signature (Figure 1C). Thus, CD47 in DLBCL can be used as a biomarker of prognosis and developed the prognostic stratification of DLBCL patients.2.EV CD47 derived from DLBCL cells has the same membrane topology as the cell surface CD47, with its extracellular domain exposed on the surface of the EVs (Figure 1D-G). Moreover, EV CD47 could function similarly to cell-surface CD47 in the suppression of macrophage phagocytosis of DLBCL cells (Figure 1H, I). DLBCL cells that had higher levels of cellular CD47 protein packaged greater amounts of CD47 into EVs, and these EVs displayed an increased binding to SIRPa of macrophages, thus inhibiting macrophage-mediated phagocytosis of DLBCL cells (Figure 1J-O).3.Antibodies against human CD47 specifically identified human CD47 on the circulating exosomes from mice bearing DLBCL xenografts but not the control mice. The level of circulating EV CD47 positively correlated with tumor size. Injection of EVs derived from DLBCL cells promoted the growth of tumors, whereas pre-treatment of the EVs with anti-CD47 antibodies (IBI188), but not IgG isotype or CD63-blocking antibodies, inhibited the effect (Figure 1P, Q).4.The presence of CD47 in the EVs isolated from the plasma of DLBCL patients, and the level of CD47 on the circulating EVs was significantly higher in DLBCL patients than that in healthy donors (Figure 1R, S). The receiver ROC curve shows that the level of circulating EV CD47 could distinguish DLBCL patients from healthy donors.ConclusionOur studies suggest that the EV CD47-SIRPa interaction may represent a critical mechanism by which DLBCL cells escape immune-mediated clearance. Our study also raises the possibility that disrupting the interaction between the EV CD47 and macrophage SIRPa is a mechanism in the CD47-SIRPa blockade-based therapies. Moreover, high levels of circulating EV CD47 would follow and correlate positively with the phagocytic activity of macrophages, and reflect the presence of a successful anti-tumor immunity elicited by the anti-CD47 therapy. Together, these findings show that EV CD47 represents an unexplored therapeutic target, which could overcome resistance to current CD47 antibody approaches. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Novel expression of zona pellucida 3 protein in normal testis; potential functional implications

The expression of the zona pellucida glycoprotein 3 (ZP3), originally thought to be specific for oocytes, was recently extended to ovarian, prostate, colorectal and lung cancers. Earlier successful ZP3 immunization of a transgenic mouse model carrying a ZP3 positive ovarian tumor emphasized the suitability of ZP3 for cancer immunotherapy. This study was carried out to determine whether any other normal tissues besides the ovary in healthy human and mouse tissues may express ZP3, considered important to exclude off-target effects of ZP3 cancer immunotherapy. Strong ZP3 expression was found in normal human and mouse testis. ZP3 protein and mRNA transcripts were localized in spermatogonia, spermatocytes and round and elongated spermatids of both human and mouse testis, as well as in a mouse spermatogonial cell line, but absent in testicular Sertoli, Leydig, spermatogonial stem and progenitor cells. All other normal human and mouse tissues were ZP3 negative. This surprising testicular ZP3 expression has implications for the development of ZP3 cancer immunotherapies, and it also alludes to the potential of using ZP3 as a target for the development of a male immunocontraceptive.

Hemagglutinin Nanoparticulate Vaccine with Controlled Photochemical Immunomodulation for Pathogenic Influenza-Specific Immunity.

Recently, viral infectious diseases, including COVID‐19 and Influenza, are the subjects of major concerns worldwide. One strategy for addressing these concerns focuses on nasal vaccines, which have great potential for achieving successful immunization via safe, easy, and affordable approaches. However, conventional nasal vaccines have major limitations resulting from fast removal when pass through nasal mucosa and mucociliary clearance hindering their effectiveness. Herein a nanoparticulate vaccine (NanoVac) exhibiting photochemical immunomodulation and constituting a new self‐assembled immunization system of a photoactivatable polymeric adjuvant with influenza virus hemagglutinin for efficient nasal delivery and antigen‐specific immunity against pathogenic influenza viruses is described. NanoVac increases the residence period of antigens and further enhances by spatiotemporal photochemical modulation in the nasal cavity. As a consequence, photochemical immunomodulation of NanoVacs successfully induces humoral and cellular immune responses followed by stimulation of mature dendritic cells, plasma cells, memory B cells, and CD4+ and CD8+ T cells, resulting in secretion of antigen‐specific immunoglobulins, cytokines, and CD8+ T cells. Notably, challenge with influenza virus after nasal immunization with NanoVacs demonstrates robust prevention of viral infection. Thus, this newly designed vaccine system can serve as a promising strategy for developing vaccines that are active against current hazardous pathogen outbreaks and pandemics.

Comparative characteristics of COVID-19 vaccines used for mass immunisation

The pandemic of the new coronavirus (COVID-19) disease that began in December 2019 in China is still having a huge impact on all spheres of human life. The herd immunity, which is the most effective tool for preventing the spread of the disease, is formed in two ways: the passive way (i.e., the formation of a population not susceptible to re-infection due to the natural spread of the disease) and the active way (mass immunisation). High rates of COVID-19 vaccination were achieved thanks to the development and mass production of new vaccines. The selection of the most promising vaccine platforms is one of the key aspects of successful mass immunisation. The aim of the study was to compare the characteristics of COVID-19 vaccines used for mass immunisation. The paper analyses the vaccine technology platforms, efficacy of different types of vaccines based on clinical trial results, safety of vaccines for different population groups, and potential for scaling up vaccine production in order to ensure the necessary vaccination coverage. The vaccines currently used for mass immunisation are: BNT162b2 (Pfizer/BioNTech), mRNA1273 (Moderna), Gam-COVID-Vac (N.F. Gamaleya National Research Center for Epidemiology and Microbiology), Ad26.COV2.S (Johnson &amp; Johnson), ChAdOx1-S (AZD1222) (AstraZeneca), BBIBP-CorV (Sinopharm), CoronaVac (Sinovac Biotech), and NVX-CoV2373 (Novavax). The comparison of the main characteristics of the vaccines demonstrated that the most promising types of vaccines for COVID-19 specific prophylaxis are RNA vaccines and recombinant adenovirus vector-based vaccines.

Вакцинопрофилактика COVID-19: оценка вклада в схемах терапии и прогноза инфекции

The article elaborates on the principles and modern methodology of evaluating vaccine safety, efficacy and effectiveness. The main parameters and criteria of successful immunization are described in plain and concise language. Special attention is paid to the analysis of clinical and epidemiological aspects of vaccination against Covid-19. The article provides the most recent epidemiological statistics on this disease. A report of the efficacy and safety of the BNT162b2 vaccine is given as an example.

Two novel SARS-CoV-2 surrogate virus neutralization assays are suitable for assessing successful immunization with mRNA-1273

BackgroundDue to large vaccination efforts with novel vaccines there is an increasing need for laboratory tests assessing successful immunizations with SARS-CoV-2 vaccines. Unfortunately classical neutralization assays are laborious, time-consuming and require an adequate biosafety level laboratory. Recently, convenient ELISA-based surrogate neutralization assays (sVNTs) for determination of neutralizing SARS-CoV-2 antibodies have been developed. Study DesignOur study compares the two novel ELISA-based SARS-CoV-2 surrogate neutralization assays “cPass SARS-CoV-2 Surrogate Virus Neutralization Test Kit” (GenScript Biotech, USA) and the “TECO SARS-CoV-2 Neutralization Antibody Assay” (TECOmedical, Switzerland) using 93 sera drawn from health care workers (HCVs) 2–3 weeks following the second vaccination with mRNA-1273 and 40 control sera from the pre-SARS-CoV-2 era before 2019. ResultsWe found a sensitivity of 100% and 91,4% and a specificity of 100% and 100% for the GenScript assay and the TECO assay, respectively. Both sVNTs show a high correlation with anti-S IgG. Moreover, both sVNTs correlate well with each other. ConclusionsSurrogate neutralization assays based on the RBD as bait feature a high specificity and sensitivity for identifying humoral neutralizing activity in individuals vaccinated with the spike-based vaccine mRNA-1273. Although these assays appear well-suited for confirming successful vaccinations with spike-based vaccines, additional studies should compare both assays regarding other purposes such as screening COVID-recovered patients or individuals vaccinated with inactivated whole virus vaccines.

Immunocontraception of male and female giraffes using the GnRH vaccine Improvac®.

The aim of this study was to develop protocols for contraception in both sexes of giraffes (Giraffa camelopardalis) by using the GnRH vaccine Improvac®. We evaluated the success of immunization by analyzing fecal reproductive hormone metabolites in female (n = 20) and male (n = 9) giraffes. Endocrine analysis provided the basis for the successful immunization protocol, as well as for assessing long‐term effects. Reliable reduction of fecal steroid metabolites to baseline levels in female giraffes was achieved with three, and in males with four or five injections at 4‐week intervals. Effective booster injections were administered at 2‐month intervals in the first year of treatment and at three to 4‐month intervals in the following years. In addition to endocrine analysis, we determined vaccination efficacy in bulls by assessing testicular atrophy. Long‐term (>2 years) use in females was often accompanied by prolonged periods of persistent corpus luteum activity, although normal cycles were not observed. Problems might occur with reversibility, because in a few males and females, even after more than 2 years since treatment had been stopped, fecal hormone metabolites have not returned to pretreatment levels. The results are somewhat ambiguous, as reproduction can be suppressed by use of Improvac®, but the question of reversibility remains unsolved.

Predictors of Vaccine Hesitancy: Implications for COVID-19 Public Health Messaging.

Objectives: Successful immunization programs require strategic communication to increase confidence among individuals who are vaccine-hesitant. This paper reviews research on determinants of vaccine hesitancy with the objective of informing public health responses to COVID-19. Method: A literature review was conducted using a broad search strategy. Articles were included if they were published in English and relevant to the topic of demographic and individual factors associated with vaccine hesitancy. Results and Discussion: Demographic determinants of vaccine hesitancy that emerged in the literature review were age, income, educational attainment, health literacy, rurality, and parental status. Individual difference factors included mistrust in authority, disgust sensitivity, and risk aversion. Conclusion: Meeting target immunization rates will require robust public health campaigns that speak to individuals who are vaccine-hesitant in their attitudes and behaviours. Based on the assortment of demographic and individual difference factors that contribute to vaccine hesitancy, public health communications must pursue a range of strategies to increase public confidence in available COVID-19 vaccines.

Considerations for successful therapeutic immunization in HIV cure.

In this special issue on human immunodeficiency (HIV) cure, we review the role of therapeutic immunization in strategies aimed to eliminate HIV-infected cells and/or mediate sustained control of viral replication in the absence of antiretroviral treatment. Recent data emerging from studies in simian immunodeficiency virus macaque models using broadly neutralizing antibodies, given alone or in combination with other immunomodulatory agents, as well as data from human clinical studies with novel therapeutic vaccines are showing encouraging results indicating that achieving viral remission or at least partial viral control of HIV without antiretroviral therapy is feasible. Although it remains unclear whether current strategies will be able to awaken a sufficient large fraction of the viral reservoir and/or vaccine-boosted immunity will induce effective, long-lasting viral suppression in chronically infected HIV population, emerging results establish cure strategies that can be further improved upon.

Anti-tumor immunity in mismatch repair-deficient colorectal cancers requires type I IFN-driven CCL5 and CXCL10.

Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor-infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8+ T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8+ T cells into dMMR CRCs strictly depend on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and type I IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be up-regulated by common chemotherapies in all CRCs, indicating that facilitating CD8+ T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs, where local priming can be maximized even in neoantigen-poor CRCs.

Universal influenza vaccine based on conserved antigens provides long-term durability of immune responses and durable broad protection against diverse challenge virus strains in mice

Current influenza vaccines rely on inducing antibody responses to the rapidly evolving hemagglutinin (HA) and neuraminidase (NA) proteins, and thus need to be strain-matched. However, predictions of strains that will circulate are imperfect, and manufacturing of new vaccines based on them takes months. As an alternative, universal influenza vaccines target highly conserved antigens. In proof of concept studies of universal vaccine candidates in animal models challenge is generally conducted only a short time after vaccination, but protective immunity lasting far longer is important for the intended public health impact. We address the challenge of providing long-term protection. We demonstrate here broad, powerful, and long-lasting immune protection for a promising universal vaccine candidate. A single intranasal dose of recombinant adenoviruses (rAd) expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) was used. Extending our previous studies of this type of vaccine, we show that antibody and T-cell responses persist for over a year without boosting, and that protection against challenge persists a year after vaccination and remains broad, covering both group 1 and 2 influenza A viruses. In addition, we extend the work to influenza B. Immunization with influenza B nucleoprotein (B/NP)-rAd also gives immune responses that last a year without boosting and protect against challenge with influenza B viruses of mismatched HA lineages. Despite host immunity to adenoviral antigens, effective readministration is possible a year after primary vaccination, as shown by successful immunization to a transgene product the animals had not seen before. Protection against challenge with divergent and highly pathogenic A/H7N9 virus was weaker but was enhanced by a second dose of vaccine. Thus, this mucosal vaccination to conserved influenza antigens confers very long-lasting immune protection in animals against a broad range of influenza A and B viruses.

Immunogenicity and Efficacy of Pneumococcal Conjugate Vaccine (Prevenar13®) in Preventing Acquisition of Carriage of Pneumococcal Vaccine Serotypes in Tanzanian Children With HIV/AIDS.

In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] –6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease.Clinical Trial Registration https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.

Production of IgY polyclonal antibody against diphtheria toxin and evaluation of its neutralization effect by Vero cell assay

BackgroundDiphtheria is a bacterial disease which is caused by Corynebacterium diphtheriae. The symptoms are due to the diphtheria toxin produced by the bacteria. Antibiotic therapy and the use of diphtheria antitoxin is a recommended strategy to control diphtheria. Although mammalian antibodies are used to treat patients, IgY antibody has advantages over mammalian ones, including cost-effectiveness and production through non-invasive means. Moreover, in contrast to mammalian antibodies, IgY does not bind to the rheumatoid factor and does not activate the complement system. The objective of this study was to evaluate the in vitro neutralizing effect of IgY against diphtheria toxin.ResultsAnti-DT IgY was produced by immunization of the laying white leghorn chickens. Indirect enzyme-linked immunosorbent assay revealed successful immunization of the animals, and the IgY was purified with a purity of 93% via polyethylene glycol precipitation method. The neutralizing activity of the purified IgY was evaluated by Vero cell viability assay. This assay confirmed that 1.95 μg (8.6 μg/ml of culture medium) of anti-DT IgY would neutralize 10 fold of cytotoxic dose 99% of DT, which was 0.3 ng (1.33 ng/ml of culture medium).ConclusionThis anti-DT IgY may be applicable for diphtheria treatment and quality controls in vaccine production.