Journal Description

Vaccines — Open Access Journal

Vaccines (ISSN 2076-393X; CODEN: VBSABP) is an international peer-reviewed open access journal published quarterly online by MDPI. The American Society for Virology (ASV) is affiliated with Vaccines and their members receive a discount on the article processing charges.

Open Access - free for readers, with article processing charges (APC) paid by authors or their institutions.
High visibility: Indexed in the Science Citation Index Expanded (SCIE) and BIOSIS Previews in Web of Science and in Scopus. Citations available in PubMed, full-text archived in PubMed Central.
CiteScore (2018 Scopus data): 5.43, which equals rank 12/272 (Q1) in the category 'Infectious Diseases', rank 31/198 (Q1) in 'Immunology' and rank 15/300 (Q1) in 'Pharmacology', among others.
Rapid publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 16.6 days after submission; acceptance to publication is undertaken in 3.9 days (median values for papers published in this journal in the second half of 2019).
Recognition of reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.

Impact Factor: 4.760 (2018)

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Latest Articles

Open AccessArticle

Human Papillomavirus (HPV) Vaccine Uptake and the Willingness to Receive the HPV Vaccination among Female College Students in China: A Multicenter Study

Dingyun You ,

Liyuan Han ,

Lian Li ,

Jingcen Hu ,

Gregory D. Zimet ,

Haridah Alias ,

Mahmoud Danaee ,

Le Cai ,

Fangfang Zeng and

Li Ping Wong

Vaccines 2020, 8(1), 31; https://doi.org/10.3390/vaccines8010031 - 16 Jan 2020

Abstract

Background: This study aimed to determine human papillomavirus (HPV) vaccine uptake and willingness to receive HPV vaccination among female college students, in China, and its associated factors. Methods: An online cross-sectional survey of female college students across the eastern, central, and western regions of China was undertaken between April and September 2019. Partial least squares structural equation modeling (PLS-SEM) was used to examine factors associated with the HPV vaccine uptake and willingness to receive the HPV vaccine. Results: Among the total 4220 students who participated in this study, 11.0% reported having been vaccinated against HPV. There are direct effects of indicators of higher socioeconomic status, older age (β = 0.084 and p = 0.006), and geographical region (residing in Eastern China, β = 0.033, and p = 0.024) on HPV vaccine uptake. Higher knowledge (β = 0.062 and p < 0.000) and perceived susceptibility (β = 0.043 and p = 0.002) were also predictors of HPV vaccine uptake. Of those who had not received the HPV vaccine, 53.5% expressed a willingness to do so. Likewise, social economic status indicators were associated with the willingness to receive the HPV vaccine. Total knowledge score (β = 0.138 and p < 0.001), both perceived susceptibility (β = 0.092 and p < 0.001) and perceived benefit (β = 0.088 and p < 0.001), and sexual experience (β = 0.041 and p = 0.007) had a positive and significant direct effect on the willingness to receive the HPV vaccine, while perceived barriers (β = −0.071 and p < 0.001) had a negative effect on the willingness to receive the HPV vaccine. Conclusions: Geographical region and socioeconomic disparities in the HPV vaccination uptake rate and willingness to receive the HPV vaccine provide valuable information for public health planning that aims to improve vaccination rates in underserved areas in China. The influence of knowledge and perceptions of HPV vaccination suggests the importance of communication for HPV immunization. Full article

(This article belongs to the Special Issue Strategies Addressing Falling Vaccine Coverage and Vaccine Hesitancy)

Open AccessEditorial

Acknowledgement to Reviewers of Vaccines in 2019

Vaccines Editorial Office

Vaccines 2020, 8(1), 30; https://doi.org/10.3390/vaccines8010030 - 16 Jan 2020

Abstract

Full article

Open AccessArticle

Surface Immunogenic Protein of Streptococcus Group B is an Agonist of Toll-Like Receptors 2 and 4 and a Potential Immune Adjuvant

Diego A. Diaz-Dinamarca ,

Ricardo A. Manzo ,

Daniel A. Soto ,

María José Avendaño-Valenzuela ,

Diego N. Bastias ,

Paulina I. Soto ,

Daniel F. Escobar ,

Valeria Vasquez-Saez ,

Flavio Carrión ,

Magdalena S. Pizarro-Ortega ,

Christian A. M. Wilson ,

Julio Berrios ,

Alexis M. Kalergis and

Abel E. Vasquez

Vaccines 2020, 8(1), 29; https://doi.org/10.3390/vaccines8010029 - 16 Jan 2020

Abstract

Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant is necessary. In this context, the use of protein Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been highlighted because of their optimal immunogenicity and minimal toxicity. The Surface Immunogenic Protein (SIP) from Group B Streptococcus (GBS) has gained importance as a new potential protein-based vaccine. Recently, we reported that recombinant SIP (rSIP) expressed by E. coli and purified by High Performance Liquid Chromatography (HPLC) alone induces a protective humoral immune response. In this study, we present the immunomodulatory properties of rSIP as a protein-based adjuvant, as an agonist of TLR. To this end, we showed that C57BL/6 bone marrow-derived dendritic cells pulsed by rSIP resulted in enhanced CD40, CD80, CD86, and Major Histocompatibility Complex (MHC) class II as well as increased secretion proinflammatory cytokines Interleukin (IL)-6, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, and IL-10. Next, we investigated the in vivo effect of rSIP in the absence or presence of ovalbumin (OVA) on antigen-specific antibody secretion in C57BL/6 mice. Immunization with rSIP plus OVA showed that anti-OVA IgG2a and IgG1a increased significantly compared with OVA alone in C57BL/6 mice. Also, the immunization of rSIP plus OVA generates increased serum cytokines levels characterized by IL-12p70, IL-10, IL-4, and IFN-γ. Interestingly, we observed that rSIP stimulate Toll Like Receptor (TLR)2 and TLR4, individually expressed by Human embryonic kidney (HEK) 293-derived TLR reporter cells. These findings suggest that rSIP is a new potential protein TLR agonist adjuvant and may be employed in the development of new vaccines. Full article

(This article belongs to the Special Issue Research on Innate Immunity and Inflammation)

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Open AccessArticle

Novel Nested Peptide Epitopes Recognized by CD4⁺ T Cells Induced by HIV-1 Conserved-Region Vaccines

Nicola Borthwick ,

Sandra Silva-Arrieta ,

Anuska Llano ,

Masafumi Takiguchi ,

Christian Brander and

Tomáš Hanke

Vaccines 2020, 8(1), 28; https://doi.org/10.3390/vaccines8010028 - 16 Jan 2020

Abstract

CD4⁺ T-cell responses play an important role in the immune control of the human immunodeficiency virus type 1 (HIV-1) infection and as such should be efficiently induced by vaccination. It follows that definition of HIV-1-derived peptides recognized by CD4⁺ T cells in association with HLA class II molecules will guide vaccine development. Here, we have characterized the fine specificity of CD4⁺ T cells elicited in human recipients of a candidate vaccine delivering conserved regions of HIV-1 proteins designated HIVconsv. The majority of these 19 most immunogenic regions contained novel epitopes, that is, epitopes not listed in the Los Alamos National Laboratory HIV Sequence Database, which were able in vitro to stimulate vaccinees’ CD4⁺ T cells to proliferate and produce interferon-γ and tumor necrosis factor-α. Accumulation of HLA class II epitopes will eventually accelerate development of HIV-1 prophylactic and therapeutic vaccines. Full article

(This article belongs to the Section HIV Vaccines)

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Open AccessArticle

Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA

Pierre Tannig ,

Antonia Sophia Peter ,

Klaus Überla and

Vaccines 2020, 8(1), 27; https://doi.org/10.3390/vaccines8010027 - 14 Jan 2020

Abstract

The importance of a balanced T_H1/T_H2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific T_H1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more T_H1/T_H2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies. Full article

(This article belongs to the Special Issue Immunization by Electroporation)

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Open AccessArticle

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

Giorgio Palù and

Vaccines 2020, 8(1), 26; https://doi.org/10.3390/vaccines8010026 - 14 Jan 2020

Abstract

: Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view. Full article

(This article belongs to the Special Issue Vaccination and Vaccine Effectiveness)

Open AccessArticle

Development and Optimization of a GMP-Compliant Manufacturing Process for a Personalized Tumor Lysate Dendritic Cell Vaccine

Caroline Boudousquié ,

Philippe O. Gannon and

Lana E. Kandalaft

Vaccines 2020, 8(1), 25; https://doi.org/10.3390/vaccines8010025 - 14 Jan 2020

Abstract

With the emergence of immune checkpoint inhibitors and adoptive T-cell therapies, there is a considerable interest in using personalized autologous dendritic cell (DC) vaccines in combination with T cell-targeting immunotherapies to potentially maximize the therapeutic impact of DC vaccines. Here, we describe the development and optimization of a Good Manufacturing Practice (GMP)-compliant manufacturing process based on tumor lysate as a tumor antigen source for the production of an oxidized tumor cell lysate loaded DC (OC-DC) vaccine. The manufacturing process required one day for lysate preparation and six days for OC-DC vaccine production. Tumor lysate production was standardized based on an optimal tumor digestion protocol and the immunogenicity was improved through oxidation using hypochloric acid prior to freeze-thaw cycles resulting in the oxidized tumor cell lysate (OC-L). Next, monocytes were selected using the CliniMACS prodigy closed system and were placed in culture in cell factories in the presence of IL-4 and GM-CSF. Immature DCs were loaded with OC-L and matured using MPLA-IFNγ. After assessing the functionality of the OC-DC cells (IL12p70 secretion and COSTIM assay), the OC-DC vaccine was cryopreserved in multiple doses for single use. Finally, the stability of the formulated doses was tested and validated. We believe this GMP-compliant DC vaccine manufacturing process will facilitate access of patients to personalized DC vaccines, and allow for multi-center clinical trials. Full article

Open AccessArticle

Cross-Protection Induced by a A/MAY/97 Emergency Vaccine Against Intra-Serotype Heterologous Challenge with a Foot-and-Mouth Disease Virus from the A/ASIA/G-VII Lineage

Aldo Dekker ,

Beatriz Sanz-Bernardo ,

Nagendrakumar Balasubramanian Singanallur ,

Anna B. Ludi ,

Jacquelyn Horsington ,

Phaedra L. Eblé ,

Donald P. King and

Wilna Vosloo

Vaccines 2020, 8(1), 24; https://doi.org/10.3390/vaccines8010024 - 14 Jan 2020

Abstract

Since 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East have been caused by a new emerging viral lineage, A/ASIA/G-VII. Invitro vaccine matching data indicated that this virus poorly matched (low r₁-value) with vaccines that were being used in the region as well as most other commercially available vaccines. The aim of this study was to assess the performance of two candidate vaccines against challenge with a representative field virus from the A/ASIA/G-VII lineage. The results from an initial full dose protection study provided encouraging data for the A/MAY/97 vaccine, while the A₂₂/IRQ/64 vaccine only protected 2/7 vaccinated animals. In view of these promising results, this vaccine was tested in a potency test (PD₅₀) experiment in which 5 cattle were vaccinated with a full dose, 5 cattle with a 1/3 dose and 5 cattle with a 1/9 dose of vaccine. At 21 days post vaccination these vaccinated cattle and 3 control cattle were challenged intradermolingually with a field isolate from the A/ASIA/G-VII lineage. The intra-serotype heterologous potency test resulted in an intra-serotype heterologous potency of 6.5 PD₅₀/dose. These data support previous studies showing that a high potency emergency vaccine can protect against clinical disease when challenged with a heterologous strain of the same serotype, indicating that not only the r₁-value of the vaccine, but also the homologous potency of a vaccine should be taken into account when advising vaccines to control an outbreak. Full article

(This article belongs to the Special Issue Development of Cross-Protective Vaccines)

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Open AccessCommunication

Polyacrylate–Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus

Mohammad Omer Faruck ,

Lili Zhao ,

Waleed M. Hussein ,

Zeinab G. Khalil ,

Robert J. Capon ,

Mariusz Skwarczynski and

Istvan Toth

Vaccines 2020, 8(1), 23; https://doi.org/10.3390/vaccines8010023 - 13 Jan 2020

Abstract

Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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Open AccessArticle

Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Zhiqiang Hu ,

Yuhong Pan ,

Anchun Cheng ,

Xingcui Zhang ,

Mingshu Wang ,

Shun Chen ,

Dekang Zhu ,

Mafeng Liu ,

Qiao Yang ,

Ying Wu ,

Xinxin Zhao ,

Juan Huang ,

Shaqiu Zhang ,

Sai Mao ,

Xumin Ou ,

Yanling Yu ,

Ling Zhang ,

Yunya Liu ,

Bin Tian ,

Leichang Pan ,

Mujeeb Ur Rehman ,

Zhongqiong Yin and

Renyong Jia

Vaccines 2020, 8(1), 22; https://doi.org/10.3390/vaccines8010022 - 13 Jan 2020

Abstract

Duck Tembusu virus (DTMUV) has recently appeared in ducks in China and the key cellular determiners for DTMUV replication in host cells remain unknown. Autophagy is an evolutionarily conserved cellular process that has been reported to facilitate flavivirus replication. In this study, we utilized primary duck embryo fibroblast (DEF) as the cell model and found that DTMUV infection triggered LC3-II increase and polyubiquitin-binding protein sequestosome 1 (p62) decrease, confirming that complete autophagy occurred in DEF cells. The induction of autophagy by pharmacological treatment increased DTMUV replication in DEF cells, whereas the inhibition of autophagy with pharmacological treatments or RNA interference decreased DTMUV replication. Inhibiting autophagy enhanced the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 7 (IRF7) pathways and increased the p62 protein level in DTMUV-infected cells. We further found that the overexpression of p62 decreased DTMUV replication and inhibited the activation of the NF-κB and IRF7 pathways, and changes in the NF-κB and IRF7 pathways were consistent with the level of phosphorylated TANK-binding kinase 1 (p-TBK1). Opposite results were found in p62 knockdown cells. In summary, we found that autophagy-mediated p62 degradation acted as a new strategy for DTMUV to evade host innate immunity. Full article

(This article belongs to the Special Issue Virus Immune Escape and Host Immune System)

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Open AccessArticle

Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Plasmodium Challenge in a Mouse Model

Kun Yun ,

Ziyang Xu ,

David B. Weiner and

Vaccines 2020, 8(1), 21; https://doi.org/10.3390/vaccines8010021 - 10 Jan 2020

Abstract

The need for a malaria vaccine is indisputable. A single vaccine for Plasmodium pre-erythrocytic stages targeting the major sporozoite antigen circumsporozoite protein (CSP) has had partial success. Additionally, CD8+ T cells targeting liver-stage (LS) antigens induced by live attenuated sporozoite vaccines were associated with protection in human challenge experiments. To further evaluate protection mediated by LS antigens, we focused on exported pre-erythrocytic proteins (exported protein 1 (EXP1), profilin (PFN), exported protein 2 (EXP2), inhibitor of cysteine proteases (ICP), transmembrane protein 21 (TMP21), and upregulated in infective sporozoites-3 (UIS3)) expressed in all Plasmodium species and designed optimized, synthetic DNA (synDNA) immunogens. SynDNA antigen cocktails were tested with and without the molecular adjuvant plasmid IL-33. Immunized animals developed robust T cell responses including induction of antigen-specific liver-localized CD8+ T cells, which were enhanced by the co-delivery of plasmid IL-33. In total, 100% of mice in adjuvanted groups and 71%–88% in non-adjuvanted groups were protected from blood-stage disease following Plasmodium yoelii sporozoite challenge. This study supports the potential of synDNA LS antigens as vaccine components for malaria parasite infection. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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Open AccessArticle

The Unknown Health Burden of Herpes Zoster Hospitalizations: The Effect on Chronic Disease Course in Adult Patients ≥50 Years

Maria Francesca Piazza ,

Andrea Orsi ,

Giancarlo Icardi and

Vaccines 2020, 8(1), 20; https://doi.org/10.3390/vaccines8010020 - 10 Jan 2020

Abstract

The effect of severe Herpes Zoster (HZ) on chronic diseases is a component of the real burden of this vaccine-preventable disease that is not commonly considered. A retrospective cohort study was conducted to assess the health burden of severe HZ in adults ≥50 years residing in Liguria Region from 2015 to 2017. Subjects hospitalized with and without HZ were matched (1:6 ratio). 437 subjects in the HZ cohort and 2622 subjects in the non-HZ cohort were enrolled. Previous immunodeficiency, autoimmune, and rare diseases are identified as main chronic conditions related to HZ hospitalization. Higher incidences of autoimmune (1.4% vs. 0.22%, p = 0.002) and gastrointestinal (7.04% vs. 3.62%, p = 0.015) diseases after hospitalization were observed in the HZ cohort compared to the non-HZ cohort. Significantly higher incidences were found after hospitalization versus the previous period for cardiovascular diseases (11.17% vs. 2.09%, p < 0.001), cerebral vasculopathy (6.13% vs. 0.60%, p < 0.001), non-arrhythmic myocardiopathy (4.31% vs. 0.59%, p = 0.002), and neuropathy (2.62% vs. 0.56%, p = 0.033). The HZ cohort showed a relative risk 10-fold higher for cerebral vasculopathy, 5-fold higher for cardiovascular diseases, and 7-fold higher for non-arrhythmic myocardiopathy. HZ causes a substantial impact on the chronic conditions. These data could suggest an implementation of HZ vaccination programs in the elderly and in high-risk groups. Full article

(This article belongs to the Special Issue Vaccination and Vaccine Effectiveness)

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Open AccessArticle

A Single Dose of Dendrimer B₂T Peptide Vaccine Partially Protects Pigs against Foot-and-Mouth Disease Virus Infection

Rodrigo Cañas-Arranz ,

Mar Forner ,

Sira Defaus ,

David Andreu and

Vaccines 2020, 8(1), 19; https://doi.org/10.3390/vaccines8010019 - 10 Jan 2020

Abstract

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals whose control relies on efficient vaccination. We have reported that dendrimer peptide B₂T, with two copies of FMDV B-cell epitope VP1 (136–154) linked through maleimide units to T-cell epitope 3A (21–35)], elicits potent B- and T-cell specific responses and confers solid protection in pigs to type-O FMDV challenge after two doses of peptide. Herein we now show that B₂T evokes specific protective immune responses after administration of a single dose of either 2 or 0.5 mg of peptide. High titers of ELISA and neutralizing antibodies against FMDV were detectable at day 15 post-immunization. Likewise, activated T cells and induced IFN-γ response to in vitro recall with FMDV peptides were also detected by the same day. Further, in 70% of B₂T-vaccinated pigs, full protection—no clinical signs of disease—was observed upon virus challenge at day 25 post-immunization. These results strengthen the potential of B₂T as a safe, cost-effective candidate vaccine conferring adequate protection against FMDV with a single dose. The finding is particularly relevant to emergency scenarios permitting only a single shot immunization. Full article

(This article belongs to the Special Issue Vaccines against RNA Viruses)

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Open AccessArticle

Alpha-Gal and Cross-Reactive Carbohydrate Determinants in the N-Glycans of Salivary Glands in the Lone Star Tick, Amblyomma americanum

Yoonseong Park ,

Donghun Kim ,

Gunavanthi D. Boorgula ,

Kristof De Schutter ,

Guy Smagghe ,

Ladislav Šimo ,

Stephanie A. Archer-Hartmann and

Parastoo Azadi

Vaccines 2020, 8(1), 18; https://doi.org/10.3390/vaccines8010018 - 09 Jan 2020

Abstract

Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal). To assess N-glycome of Amblyomma americanum, we examined the N-glycan structures in male and female salivary glands at three different feeding stages and in carcasses of partially fed lone star ticks. We also surveyed the genes involved in the N-glycosylation in the tick species. The aGal epitopes and cross-reactive carbohydrate determinants (CCD) increases over time after the onset of blood feeding in both male and female A. americanum. These CCDs include xylosylation of the core mannose, 1,3-mono and 1,3- and 1,6-difucosylations of the basal GlcNac and mono- or diantennary aGal. Combinations of both xylosylation and aGal and fucosylation and aGal were also found on the N-glycan structures. While the enzymes required for the early steps of the N-glycosylation pathway are quite conserved, the enzymes involved in the later stages of N-glycan maturation in the Golgi apparatus are highly diverged from those of insects. Most of all, we propose that the aGal serves as a molecular mimicry of bioactive proteins during tick feedings on mammalian hosts, while it contributes as a sensitizer of allergy in atypical host human. Full article

(This article belongs to the Special Issue Arthropod Ectoparasites and Associated Diseases)

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Open AccessArticle

Protection Efficacy of Oral Bait Probiotic Vaccine Constitutively Expressing Tetravalent Toxoids against Clostridium perfringens Exotoxins in Livestock (Rabbits)

Jing Bai ,

Xinyuan Qiao ,

Yingying Ma ,

Meijing Han ,

Shuo Jia ,

Xinning Huang ,

Bing Han ,

Li Wang ,

Yijing Li and

Yigang Xu

Vaccines 2020, 8(1), 17; https://doi.org/10.3390/vaccines8010017 - 08 Jan 2020

Abstract

Clostridium perfringens is an opportunistic pathogen. Its main virulence factors are exotoxins, which are the etiological agents of enteritis necroticans and enterotoxemia caused in livestock (cattle, sheep, and rabbits). Here, we demonstrated effective immune protection for rabbits against α, β, and ε exotoxins of C. perfringens provided by an oral tetravalent bait probiotic vaccine delivering α, ε, β1, and β2 toxoids of C. perfringens. Results showed that the recombinant probiotic had good segregational stability and good colonization ability in the rabbit intestinal tract. Oral administration of the probiotic vaccine can effectively elicit significant levels of antigen-specific mucosa sIgA and sera IgG antibodies with exotoxin-neutralizing activity. Additionally, oral immunization with the probiotic vaccine effectively promoted lymphoproliferation and Th1/Th2-associated cytokine production. The protection rate of immunized rabbits with the probiotic vaccine was 80% after challenging rabbits with a combination of C. perfringens (toxinotypes A, C, and D) and exotoxin mixture, which was better than the 60% provided by a commercial inactivated C. perfringens A, C, and D trivalent vaccine. Moreover, obvious histopathological changes were observed in the intestinal tissues of rabbits in the commercial vaccine and PBS groups. The bait probiotic vaccine can provide effective protection against C. perfringens exotoxins, suggesting a promising C. perfringens vaccination strategy. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

Open AccessArticle

Toxoplasma gondii ADSL Knockout Provides Excellent Immune Protection against a Variety of Strains

Luyao Wang ,

Ding Tang ,

Chenghang Yang ,

Jing Yang and

Rui Fang

Vaccines 2020, 8(1), 16; https://doi.org/10.3390/vaccines8010016 - 06 Jan 2020

Abstract

Toxoplasma gondii is a protozoan parasite, occurring worldwide, endangers human health and causes enormous economic losses to the Ministry of Agriculture. A safe and effective vaccination is needed to handle these problems. In addition, ideal vaccine production is a challenge in the future. In this study, we knocked out the adenylosuccinate lyase (ADSL) gene and found that the gene reduces the growth rate of T. gondii tachyzoites in vitro under standard growth conditions by plaque or replication experiments. Furthermore, mice that were immunized with tachyzoites of the ME49ΔADSL strain induced 100% protection efficacy against challenge with the type 1 strain RH, type 2 strain ME49 and type 3 strain VEG. All mice that were immunized with ME49ΔADSL had a survival rate of 100% when they were reinfected with wild-type strains, either 30 days or 70 days after immunization, and immunization was also protective against homologous infection with 50 T. gondii ME49 tissue cysts. In addition, the level of Toxoplasma-specific IgG was significantly elevated at 30 and 70 days after immunization. ME49ΔADSL induced high levels of Th1 cytokines (interferon gamma (IFN-γ), interleukin (IL)-12) at 4 weeks after immunization and spleen cell cultures from mice vaccinated for 150 days were able to produce robust INF-γ and IL-12 levels in the supernatant. The results of the present study showed that ΔADSL vaccination induced a T. gondii-specific cellular immune response against further infections. These results suggest that the ADSL-deficient vaccine can induce anti-Toxoplasma gondii humoral and cellular immune responses and has 100% immune protection against post-challenge by the type 1 strain RH, type 2 strain ME49 and type 3 strain VEG. It will be used as an excellent candidate for live vaccines and may contribute in a positive meaning to control human toxoplasmosis. Full article

(This article belongs to the Special Issue Genomic medicine and advances in Vaccine technology and development in the developing and developed world)

Open AccessArticle

Epidemiology of Respiratory Syncytial Virus-Related Hospitalization Over a 5-Year Period in Italy: Evaluation of Seasonality and Age Distribution Before Vaccine Introduction

Giuseppe Indolfi and

Vaccines 2020, 8(1), 15; https://doi.org/10.3390/vaccines8010015 - 04 Jan 2020

Abstract

Respiratory Syncytial Virus (RSV) is associated with most of the acute viral respiratory tract infections causing hospitalization with a peak during the first months of life. Many clinical trials of RSV vaccine candidates are being carried out. The aim of this study was to obtain epidemiologic information to give suggestions on target populations and prevention strategies before the introduction of new vaccines or monoclonal antibodies. We retrospectively evaluated, over a 5-year period (September 2014–August 2019), a population of hospitalized Italian children aged 0–6 years with a laboratory confirmed diagnosis of RSV infection. Risk factors, seasonality of RSV infection, distribution according to age, cases of coinfections and reinfections and cases needing Intensive Care Unit were evaluated. Hospitalizations due to RSV were 624 in the period under study. The peak was found between November and April, with 80.4% of cases recorded between December and February. 62.5% of cases were found in children under three months of age and 41% in children under 30 days old. The need for intensive care was associated with younger ages, with 70.9% of cases in children below three months of age. Unless the incoming vaccines demonstrate a strong herd protection effect, preventive strategies should be aimed at newborns or at maternal immunization. Full article

(This article belongs to the Special Issue Strategies Addressing Falling Vaccine Coverage and Vaccine Hesitancy)

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Open AccessArticle

Evaluation of Passive Immunity Induced by Immunisation Using Two Inactivated gE-deleted Marker Vaccines against Infectious Bovine Rhinotracheitis (IBR) in Calves

Paola Gobbi ,

Claudia Pellegrini and

Gian Mario De Mia

Vaccines 2020, 8(1), 14; https://doi.org/10.3390/vaccines8010014 - 04 Jan 2020

Abstract

Different types of vaccines against Infectious Bovine Rhinotracheitis (IBR) are commercially available. Among these, inactivated glycoprotein E (gE)-deleted marker vaccines are commonly used, but their ability to induce passive immunity is poorly known. Here, we evaluated the passive immunity transferred from dams immunised with commercial inactivated gE-deleted marker vaccines to calves. We vaccinated 12 pregnant cattle devoid of neutralising antibodies against Bovine alphaherpesvirus 1 (BoHV-1) and divided them into two groups with 6 animals each. Both groups were injected with a different inactivated gE-deleted marker vaccine administrated via intranasal or intramuscular routes. An additional 6 pregnant cattle served as the unvaccinated control group. After calving, the number of animals in each group was increased by the newborn calves. In the dams, the humoral immune response was evaluated before calving and, subsequently, at different times until post-calving day 180 (PCD180). In addition, the antibodies in colostrum, milk, and in serum samples from newborn calves were evaluated at different times until PCD180. The results indicated that inactivated glycoprotein E (gE)-deleted marker vaccines are safe and produce a good humoral immune response in pregnant cattle until calving and PCD180. Moreover, results showed that, in calf serum, passive immunity persists until PCD180. Full article

(This article belongs to the Special Issue Herpesvirus Vaccines)

Open AccessReview

Exploiting B Cell Receptor Analyses to Inform on HIV-1 Vaccination Strategies

Christoph Kreer ,

Henning Gruell ,

Thierry Mora ,

Aleksandra M. Walczak and

Florian Klein

Vaccines 2020, 8(1), 13; https://doi.org/10.3390/vaccines8010013 - 01 Jan 2020

Abstract

The human antibody repertoire is generated by the recombination of different gene segments as well as by processes of somatic mutation. Together these mechanisms result in a tremendous diversity of antibodies that are able to combat various pathogens including viruses and bacteria, or malignant cells. In this review, we summarize the opportunities and challenges that are associated with the analyses of the B cell receptor repertoire and the antigen-specific B cell response. We will discuss how recent advances have increased our understanding of the antibody response and how repertoire analyses can be exploited to inform on vaccine strategies, particularly against HIV-1. Full article

(This article belongs to the Special Issue Advances in Antibody-based HIV-1 Vaccine Development)

Open AccessReview

Safety of Co-Administration Versus Separate Administration of the Same Vaccines in Children: A Systematic Literature Review

Nino Künzli and

Vaccines 2020, 8(1), 12; https://doi.org/10.3390/vaccines8010012 - 31 Dec 2019

Abstract

The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate (DTaP-HepB-IPV/Hib) vaccine, measles, mumps, and rubella (MMR) vaccine, and pneumococcal conjugate 7-valent (PCV7) or 13-valent (PCV13) vaccines. Of this, 16% (n = 8) of the studies reported significantly more adverse events following immunization (AEFI) while in 10% (n = 5) significantly fewer adverse events were found in the co-administration groups. Statistically significant differences between co-administration and separate administration were found for 16 adverse events, for 11 different vaccine co-administrations. In general, studies briefly described safety and one-third of studies lacked any statistical assessment of AEFI. Overall, the evidence on the safety of vaccine co-administrations compared to separate vaccine administrations is inconclusive and there is a paucity of large post-licensure studies addressing this issue. Full article

(This article belongs to the Special Issue Strategies Addressing Falling Vaccine Coverage and Vaccine Hesitancy)