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15 pages, 2711 KiB

Open AccessArticle

Local Enrichment with Convergence of Enriched T-Cell Clones Are Hallmarks of Effective Peptide Vaccination against B16 Melanoma

by Anna Vyacheslavovna Izosimova, Alexandra Valerievna Shabalkina, Mikhail Yurevich Myshkin, Elizaveta Viktorovna Shurganova, Daria Sergeevna Myalik, Ekaterina Olegovna Ryzhichenko, Alina Faritovna Samitova, Ekaterina Vladimirovna Barsova, Irina Aleksandrovna Shagina, Olga Vladimirovna Britanova, Diana Vladimirovna Yuzhakova and George Vladimirovich Sharonov

Vaccines 2024, 12(4), 345; https://doi.org/10.3390/vaccines12040345 - 22 Mar 2024

Viewed by 686

Abstract

Background: Some peptide anticancer vaccines elicit a strong T-cell memory response but fail to suppress tumor growth. To gain insight into tumor resistance, we compared two peptide vaccines, p20 and p30, against B16 melanoma, with both exhibiting good in vitro T-cell responses but [...] Read more.

Background: Some peptide anticancer vaccines elicit a strong T-cell memory response but fail to suppress tumor growth. To gain insight into tumor resistance, we compared two peptide vaccines, p20 and p30, against B16 melanoma, with both exhibiting good in vitro T-cell responses but different tumor suppression abilities. Methods: We compared activation markers and repertoires of T-lymphocytes from tumor-draining (dLN) and non-draining (ndLN) lymph nodes for the two peptide vaccines. Results: We showed that the p30 vaccine had better tumor control as opposed to p20. p20 vaccine induced better in vitro T-cell responsiveness but failed to suppress tumor growth. Efficient antitumor vaccination is associated with a higher clonality of cytotoxic T-cells (CTLs) in dLNs compared with ndLNs and the convergence of most of the enriched clones. With the inefficient p20 vaccine, the most expanded and converged were clones of the bystander T-cells without an LN preference. Conclusions: Here, we show that the clonality and convergence of the T-cell response are the hallmarks of efficient antitumor vaccination. The high individual and methodological dependencies of these parameters can be avoided by comparing dLNs and ndLNs. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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16 pages, 2211 KiB

Open AccessArticle

A Recombinant Multivalent Vaccine (rCpa1) Induces Protection for C57BL/6 and HLA Transgenic Mice against Pulmonary Infection with Both Species of Coccidioides

by Althea Campuzano, Komali Devi Pentakota, Yu-Rou Liao, Hao Zhang, Nathan P. Wiederhold, Gary R. Ostroff and Chiung-Yu Hung

Vaccines 2024, 12(1), 67; https://doi.org/10.3390/vaccines12010067 - 09 Jan 2024

Cited by 1 | Viewed by 953

Abstract

Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci), which have a 4–5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) [...] Read more.

Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci), which have a 4–5% difference in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from Cp isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1-based vaccine against both species of Coccidioides. DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of Cp and Ci, respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against five highly virulent isolates of Cp and Ci. There are total of seven amino acid substitutions in the rCpa1 antigen between Cp and Ci. Both C57BL/6 and HLA-DR4 mice that were vaccinated with an rCpa1 vaccine had a significant reduction of fungal burden and increased numbers of IFN-γ- and IL-17-producing CD4+ T cells in the first 2 weeks post challenge. These data suggest that rCpa1 has cross-protection activity against Cp and Ci pulmonary infection through activation of early Th1 and Th17 responses. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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16 pages, 3544 KiB

Open AccessArticle

Development of A Standardized Opsonophagocytosis Killing Assay for Group B Streptococcus and Assessment in an Interlaboratory Study

by Stephanie Leung, Clare F. Collett, Lauren Allen, Suzanna Lim, Pete Maniatis, Shanna J. Bolcen, Bailey Alston, Palak Y. Patel, Gaurav Kwatra, Tom Hall, Stephen Thomas, Stephen Taylor, Kirsty Le Doare and Andrew Gorringe

Vaccines 2023, 11(11), 1703; https://doi.org/10.3390/vaccines11111703 - 09 Nov 2023

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Abstract

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, [...] Read more.

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65–3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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20 pages, 3561 KiB

Open AccessArticle

In Silico Analyses, Experimental Verification and Application in DNA Vaccines of Ebolavirus GP-Derived pan-MHC-II-Restricted Epitopes

by Junqi Zhang, Baozeng Sun, Wenyang Shen, Zhenjie Wang, Yang Liu, Yubo Sun, Jiaxing Zhang, Ruibo Liu, Yongkai Wang, Tianyuan Bai, Zilu Ma, Cheng Luo, Xupeng Qiao, Xiyang Zhang, Shuya Yang, Yuanjie Sun, Dongbo Jiang and Kun Yang

Vaccines 2023, 11(10), 1620; https://doi.org/10.3390/vaccines11101620 - 20 Oct 2023

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Abstract

(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host [...] Read more.

(1) Background and Purpose: Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), which causes extremely high mortality and widespread epidemics. The only glycoprotein (GP) on the surface of EBOV particles is the key to mediating viral invasion into host cells. DNA vaccines for EBOV are in development, but their effectiveness is unclear. The lack of immune characteristics resides in antigenic MHC class II reactivity. (2) Methods: We selected MHC-II molecules from four human leukocyte antigen II (HLA-II) superfamilies with 98% population coverage and eight mouse H2-I alleles. IEDB, NetMHCIIpan, SYFPEITHI, and Rankpep were used to screen MHC-II-restricted epitopes with high affinity for EBOV GP. Further immunogenicity and conservation analyses were performed using VaxiJen and BLASTp, respectively. EpiDock was used to simulate molecular docking. Cluster analysis and binding affinity analysis of EBOV GP epitopes and selected MHC-II molecules were performed using data from NetMHCIIpan. The selective GP epitopes were verified by the enzyme-linked immunospot (ELISpot) assay using splenocytes of BALB/c (H2d), C3H, and C57 mice after DNA vaccine pVAX-GP_EBO immunization. Subsequently, BALB/c mice were immunized with Protein-GP_EBO, plasmid pVAX-GP_EBO, and pVAX-LAMP/GP_EBO, which encoded EBOV GP. The dominant epitopes of BALB/c (H-2-I-AdEd genotype) mice were verified by the enzyme-linked immunospot (ELISpot) assay. It is also used to evaluate and explore the advantages of pVAX-LAMP/GP_EBO and the reasons behind them. (3) Results: Thirty-one HLA-II-restricted and 68 H2-I-restricted selective epitopes were confirmed to have high affinity, immunogenicity, and conservation. Nineteen selective epitopes have cross-species reactivity with good performance in MHC-II molecular docking. The ELISpot results showed that pVAX-GP_EBO could induce a cellular immune response to the synthesized selective peptides. The better immunoprotection of the DNA vaccines pVAX-LAMP/GP_EBO coincides with the enhancement of the MHC class II response. (4) Conclusions: Promising MHC-II-restricted candidate epitopes of EBOV GP were identified in humans and mice, which is of great significance for the development and evaluation of Ebola vaccines. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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14 pages, 3543 KiB

Open AccessArticle

Influenza H7N9 Virus Hemagglutinin with T169A Mutation Possesses Enhanced Thermostability and Provides Effective Immune Protection against Lethal H7N9 Virus Challenge in Chickens

by Taoran Chen, Dexin Kong, Xiaolong Hu, Yinze Gao, Shaorong Lin, Ming Liao and Huiying Fan

Vaccines 2023, 11(8), 1318; https://doi.org/10.3390/vaccines11081318 - 02 Aug 2023

Cited by 1 | Viewed by 1238

Abstract

H7N9 avian influenza virus (AIV) has caused huge losses in the poultry industry and impacted human public health security, and still poses a potential threat. Currently, immune prevention and control of avian influenza relies on traditional inactivated vaccines; however, they have some limitations [...] Read more.

H7N9 avian influenza virus (AIV) has caused huge losses in the poultry industry and impacted human public health security, and still poses a potential threat. Currently, immune prevention and control of avian influenza relies on traditional inactivated vaccines; however, they have some limitations and genetically engineered avian influenza subunit vaccines may be potential candidate vaccines. In this study, a T169A mutation in the HA protein derived from H7N9 AIV A/Chicken/Guangdong/16876 (H7N9-16876) was generated using the baculovirus expression system (BVES). The results showed that the mutant (HAm) had significantly increased thermostability compared with the wild-type HA protein (HA-WT). Importantly, immunizing chickens with HAm combined with ISA 71VG elicited higher cross-reactive hemagglutination inhibition (HI) antibody responses and cytokine (IFN-γ and IL-4) secretion. After a lethal challenge with heterologous H7N9 AIV, the vaccine conferred chickens with 100% (10/10) clinical protection and effectively inhibited viral shedding, with 90% (9/10) of the chickens showing no virus shedding. The thermostability of HAm may represent an advantage in practical vaccine manufacture and application. In general, the HAm generated in this study represents a promising subunit vaccine candidate for the prevention and control of H7N9 avian influenza. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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Review

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40 pages, 2342 KiB

Open AccessReview

Nanoparticles and Antiviral Vaccines

by Sen Liu, Meilin Hu, Xiaoqing Liu, Xingyu Liu, Tao Chen, Yiqiang Zhu, Taizhen Liang, Shiqi Xiao, Peiwen Li and Xiancai Ma

Vaccines 2024, 12(1), 30; https://doi.org/10.3390/vaccines12010030 - 27 Dec 2023

Viewed by 2147

Abstract

Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to [...] Read more.

Viruses have threatened human lives for decades, causing both chronic and acute infections accompanied by mild to severe symptoms. During the long journey of confrontation, humans have developed intricate immune systems to combat viral infections. In parallel, vaccines are invented and administrated to induce strong protective immunity while generating few adverse effects. With advancements in biochemistry and biophysics, different kinds of vaccines in versatile forms have been utilized to prevent virus infections, although the safety and effectiveness of these vaccines are diverse from each other. In this review, we first listed and described major pathogenic viruses and their pandemics that emerged in the past two centuries. Furthermore, we summarized the distinctive characteristics of different antiviral vaccines and adjuvants. Subsequently, in the main body, we reviewed recent advances of nanoparticles in the development of next-generation vaccines against influenza viruses, coronaviruses, HIV, hepatitis viruses, and many others. Specifically, we described applications of self-assembling protein polymers, virus-like particles, nano-carriers, and nano-adjuvants in antiviral vaccines. We also discussed the therapeutic potential of nanoparticles in developing safe and effective mucosal vaccines. Nanoparticle techniques could be promising platforms for developing broad-spectrum, preventive, or therapeutic antiviral vaccines. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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13 pages, 1512 KiB

Open AccessReview

The Application of Mesenchymal Stem Cells in Future Vaccine Synthesis

by Rui Zhang, Xingxiang Duan, Ye Liu, Jia Xu, Abdullkhaleg Ali Ghaleb Al-bashari, Peng Ye, Qingsong Ye and Yan He

Vaccines 2023, 11(11), 1631; https://doi.org/10.3390/vaccines11111631 - 24 Oct 2023

Viewed by 1181

Abstract

Vaccines have significant potential in treating and/or preventing diseases, yet there remain challenges in developing effective vaccines against some diseases, such as AIDS and certain tumors. Mesenchymal stem cells (MSCs), a subset of cells with low immunogenicity, high proliferation potential, and an abundant [...] Read more.

Vaccines have significant potential in treating and/or preventing diseases, yet there remain challenges in developing effective vaccines against some diseases, such as AIDS and certain tumors. Mesenchymal stem cells (MSCs), a subset of cells with low immunogenicity, high proliferation potential, and an abundant source of extracellular vesicles (EVs), represent one of the novel and promising vaccine platforms. This review describes the unique features and potential mechanisms of MSCs as a novel vaccine platform. We also cover aspects such as the safety and stability of MSCs that warrant future in-depth studies. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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11 pages, 919 KiB

Open AccessReview

Immune Imprinting and Implications for COVID-19

by Zhiqian Zhou, Julia Barrett and Xuan He

Vaccines 2023, 11(4), 875; https://doi.org/10.3390/vaccines11040875 - 20 Apr 2023

Cited by 10 | Viewed by 3831

Abstract

Immunological memory is the key source of protective immunity against pathogens. At the current stage of the COVID-19 pandemic, heterologous combinations of exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, the downside of memory, might limit [...] Read more.

Immunological memory is the key source of protective immunity against pathogens. At the current stage of the COVID-19 pandemic, heterologous combinations of exposure to viral antigens during infection and/or vaccination shape a distinctive immunological memory. Immune imprinting, the downside of memory, might limit the generation of de novo immune response against variant infection or the response to the next-generation vaccines. Here, we review mechanistic basis of immune imprinting by focusing on B cell immunobiology and discuss the extent to which immune imprinting is harmful, as well as its effect on SARS-CoV-2 infection and vaccination. Full article

(This article belongs to the Special Issue Immune Correlates of Protection in Vaccines)

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