Editorial

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2 pages, 164 KiB

Open AccessEditorial

Special Issue “Virus-Like Particle Vaccines”

by Monique Vogel and Martin F. Bachmann

Viruses 2020, 12(8), 872; https://doi.org/10.3390/v12080872 - 10 Aug 2020

Cited by 2 | Viewed by 2695

Abstract

Virus-like particles (VLPs) have become a key tool for vaccine developers and manufacturers [...] Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

Research

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19 pages, 3325 KiB

Open AccessArticle

Immunization of Cats against Fel d 1 Results in Reduced Allergic Symptoms of Owners

by Franziska Thoms, Stefanie Haas, Aline Erhart, Claudia S. Nett, Silvia Rüfenacht, Nicole Graf, Arnis Strods, Gauravraj Patil, Thonur Leenadevi, Michael C. Fontaine, Lindsey A. Toon, Gary T. Jennings, Gabriela Senti, Thomas M. Kündig and Martin F. Bachmann

Viruses 2020, 12(3), 288; https://doi.org/10.3390/v12030288 - 06 Mar 2020

Cited by 16 | Viewed by 6557

Abstract

An innovative approach was tested to treat cat allergy in humans by vaccinating cats with Fel-CuMV (HypoCat^TM), a vaccine against the major cat allergen Fel d 1 based on virus-like particles derived from cucumber mosaic virus (CuMV-VLPs). Upon vaccination, cats develop [...] Read more.

An innovative approach was tested to treat cat allergy in humans by vaccinating cats with Fel-CuMV (HypoCat^TM), a vaccine against the major cat allergen Fel d 1 based on virus-like particles derived from cucumber mosaic virus (CuMV-VLPs). Upon vaccination, cats develop neutralizing antibodies against the allergen Fel d 1, which reduces the level of reactive allergen, thus lowering the symptoms or even preventing allergic reactions in humans. The combined methodological field study included ten cat-allergic participants who lived together with their cats (n = 13), that were immunized with Fel-CuMV. The aim was to determine methods for measuring a change in allergic symptoms. A home-based provocation test (petting time and organ specific symptom score (OSSS)) and a general weekly (or monthly) symptom score (G(W)SS) were used to assess changes in allergic symptoms. The petting time until a pre-defined level of allergic symptoms was reached increased already early after vaccination of the cats and was apparent over the course of the study. In addition, the OSSS after provocation and G(W)SS recorded a persistent reduction in symptoms over the study period and could serve for long-term assessment. Hence, the immunization of cats with HypoCat^TM (Fel-CuMV) may have a positive impact on the cat allergy of the owner, and changes could be assessed by the provocation test as well as G(W)SS. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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24 pages, 8399 KiB

Open AccessArticle

Quality Assessment of Virus-Like Particles at Single Particle Level: A Comparative Study

by Irene González-Domínguez, Eduard Puente-Massaguer, Laura Cervera and Francesc Gòdia

Viruses 2020, 12(2), 223; https://doi.org/10.3390/v12020223 - 17 Feb 2020

Cited by 28 | Viewed by 6260

Abstract

Virus-like particles (VLPs) have emerged as a powerful scaffold for antigen presentation and delivery strategies. Compared to single protein-based therapeutics, quality assessment requires a higher degree of refinement due to the structure of VLPs and their similar properties to extracellular vesicles (EVs). Advances [...] Read more.

Virus-like particles (VLPs) have emerged as a powerful scaffold for antigen presentation and delivery strategies. Compared to single protein-based therapeutics, quality assessment requires a higher degree of refinement due to the structure of VLPs and their similar properties to extracellular vesicles (EVs). Advances in the field of nanotechnology with single particle and high-resolution analysis techniques provide appealing approaches to VLP characterization. In this study, six different biophysical methods have been assessed for the characterization of HIV-1-based VLPs produced in mammalian and insect cell platforms. Sample preparation and equipment set-up were optimized for the six strategies evaluated. Electron Microscopy (EM) disclosed the presence of several types of EVs within VLP preparations and cryogenic transmission electron microscopy (cryo-TEM) resulted in the best technique to resolve the VLP ultrastructure. The use of super-resolution fluorescence microscopy (SRFM), nanoparticle tracking analysis (NTA) and flow virometry enabled the high throughput quantification of VLPs. Interestingly, differences in the determination of nanoparticle concentration were observed between techniques. Moreover, NTA and flow virometry allowed the quantification of both EVs and VLPs within the same experiment while analyzing particle size distribution (PSD), simultaneously. These results provide new insights into the use of different analytical tools to monitor the production of nanoparticle-based biologicals and their associated contaminants. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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15 pages, 2189 KiB

Open AccessArticle

A Chimeric Sudan Virus-Like Particle Vaccine Candidate Produced by a Recombinant Baculovirus System Induces Specific Immune Responses in Mice and Horses

by Fangfang Wu, Shengnan Zhang, Ying Zhang, Ruo Mo, Feihu Yan, Hualei Wang, Gary Wong, Hang Chi, Tiecheng Wang, Na Feng, Yuwei Gao, Xianzhu Xia, Yongkun Zhao and Songtao Yang

Viruses 2020, 12(1), 64; https://doi.org/10.3390/v12010064 - 03 Jan 2020

Cited by 6 | Viewed by 3355

Abstract

Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of [...] Read more.

Ebola virus infections lead to severe hemorrhagic fevers in humans and nonhuman primates; and human fatality rates are as high as 67%–90%. Since the Ebola virus was discovered in 1976, the only available treatments have been medical support or the emergency administration of experimental drugs. The absence of licensed vaccines and drugs against the Ebola virus impedes the prevention of viral infection. In this study, we generated recombinant baculoviruses (rBV) expressing the Sudan virus (SUDV) matrix structural protein (VP40) (rBV-VP40-VP40) or the SUDV glycoprotein (GP) (rBV-GP-GP), and SUDV virus-like particles (VLPs) were produced by co-infection of Sf9 cells with rBV-SUDV-VP40 and rBV-SUDV-GP. The expression of SUDV VP40 and GP in SUDV VLPs was demonstrated by IFA and Western blot analysis. Electron microscopy results demonstrated that SUDV VLPs had a filamentous morphology. The immunogenicity of SUDV VLPs produced in insect cells was evaluated by the immunization of mice. The analysis of antibody responses showed that mice vaccinated with SUDV VLPs and the adjuvant Montanide ISA 201 produced SUDV GP-specific IgG antibodies. Sera from SUDV VLP-immunized mice were able to block infection by SUDV GP pseudotyped HIV, indicating that a neutralizing antibody against the SUDV GP protein was produced. Furthermore, the activation of B cells in the group immunized with VLPs mixed with Montanide ISA 201 was significant one week after the primary immunization. Vaccination with the SUDV VLPs markedly increased the frequency of antigen-specific cells secreting type 1 and type 2 cytokines. To study the therapeutic effects of SUDV antibodies, horses were immunized with SUDV VLPs emulsified in Freund’s complete adjuvant or Freund’s incomplete adjuvant. The results showed that horses could produce SUDV GP-specific antibodies and neutralizing antibodies. These results showed that SUDV VLPs demonstrate excellent immunogenicity and represent a promising approach for vaccine development against SUDV infection. Further, these horse anti-SUDV purified immunoglobulins lay a foundation for SUDV therapeutic drug research. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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14 pages, 2977 KiB

Open AccessArticle

Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization

by Maria Malm, Timo Vesikari and Vesna Blazevic

Viruses 2019, 11(11), 1018; https://doi.org/10.3390/v11111018 - 02 Nov 2019

Cited by 9 | Viewed by 3579

Abstract

Human noroviruses (NoVs) are a genetically diverse, constantly evolving group of viruses. Here, we studied the effect of NoV pre-existing immunity on the success of NoV vaccinations with genetically close and distant genotypes. A sequential immunization as an alternative approach to multivalent NoV [...] Read more.

Human noroviruses (NoVs) are a genetically diverse, constantly evolving group of viruses. Here, we studied the effect of NoV pre-existing immunity on the success of NoV vaccinations with genetically close and distant genotypes. A sequential immunization as an alternative approach to multivalent NoV virus-like particles (VLPs) vaccine was investigated. Mice were immunized with NoV GI.3, GII.4-1999, GII.17, and GII.4 Sydney as monovalent VLPs or as a single tetravalent mixture combined with rotavirus VP6-protein. Sequentially immunized mice were primed with a trivalent vaccine candidate (GI.3 + GII.4-1999 + VP6) and boosted, first with GII.17 and then with GII.4 Sydney VLPs. NoV serum antibodies were analyzed. Similar NoV genotype-specific immune responses were induced with the monovalent and multivalent mixture immunizations, and no immunological interference was observed. Multivalent immunization with simultaneous mix was found to be superior to sequential immunization, as sequential boost induced strong blocking antibody response against the distant genotype (GII.17), but not against GII.4 Sydney, closely related to GII.4-1999, contained in the priming vaccine. Genetically close antigens may interfere with the immune response generation and thereby immune responses may be differently formed depending on the degree of NoV VLP genotype identity. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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10 pages, 936 KiB

Open AccessArticle

Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak

by Arturo Cérbulo-Vázquez, Lourdes Arriaga-Pizano, Gabriela Cruz-Cureño, Ilka Boscó-Gárate, Eduardo Ferat-Osorio, Rodolfo Pastelin-Palacios, Ricardo Figueroa-Damian, Denisse Castro-Eguiluz, Javier Mancilla-Ramirez, Armando Isibasi and Constantino López-Macías

Viruses 2019, 11(9), 868; https://doi.org/10.3390/v11090868 - 17 Sep 2019

Cited by 2 | Viewed by 3471

Abstract

The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine [...] Read more.

The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 μg dose of VLP vaccine, or (3) 45 μg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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Review

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18 pages, 1576 KiB

Open AccessReview

Influenza Virus Like Particles (VLPs): Opportunities for H7N9 Vaccine Development

by Peter Pushko and Irina Tretyakova

Viruses 2020, 12(5), 518; https://doi.org/10.3390/v12050518 - 08 May 2020

Cited by 28 | Viewed by 5672

Abstract

In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and [...] Read more.

In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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20 pages, 1244 KiB

Open AccessReview

Virus-Like Particles as an Immunogenic Platform for Cancer Vaccines

by Jerri C. Caldeira, Michael Perrine, Federica Pericle and Federica Cavallo

Viruses 2020, 12(5), 488; https://doi.org/10.3390/v12050488 - 27 Apr 2020

Cited by 40 | Viewed by 5236

Abstract

Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic [...] Read more.

Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic or chemical conjugation facilitates the multivalent display of a homologous or heterologous epitope. Most VLP range in diameter from 25 to 100 nm and, in most cases, drain freely into the lymphatic vessels and induce antibodies with high titers and affinity without the need for additional adjuvants. VLP administration can be performed using different strategies, regimens, and doses to improve the immunogenicity of the antigen they expose on their surface. This article summarizes the features of VLP and presents them as a relevant platform technology to address not only infectious diseases but also chronic diseases and cancer. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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10 pages, 1102 KiB

Open AccessReview

Virus-Like Particle-Mediated Vaccination against Interleukin-13 May Harbour General Anti-Allergic Potential beyond Atopic Dermatitis

by John Foerster and Aleksandra Molęda

Viruses 2020, 12(4), 438; https://doi.org/10.3390/v12040438 - 13 Apr 2020

Cited by 4 | Viewed by 3118

Abstract

Virus-like particle (VLP)-based anti-infective prophylactic vaccination has been established in clinical use. Although validated in proof-of-concept clinical trials in humans, no VLP-based therapeutic vaccination against self-proteins to modulate chronic disease has yet been licensed. The present review summarises recent scientific advances, identifying interleukin-13 [...] Read more.

Virus-like particle (VLP)-based anti-infective prophylactic vaccination has been established in clinical use. Although validated in proof-of-concept clinical trials in humans, no VLP-based therapeutic vaccination against self-proteins to modulate chronic disease has yet been licensed. The present review summarises recent scientific advances, identifying interleukin-13 as an excellent candidate to validate the concept of anti-cytokine vaccination. Based on numerous clinical studies, long-term elimination of IL-13 is not expected to trigger target-related serious adverse effects and is likely to be safer than combined targeting of IL-4/IL-13. Furthermore, recently published results from large-scale trials confirm that elimination of IL-13 is highly effective in atopic dermatitis, an exceedingly common condition, as well as eosinophilic esophagitis. The distinctly different mode of action of a polyclonal vaccine response is discussed in detail, suggesting that anti-IL-13 vaccination has the potential of outperforming monoclonal antibody-based approaches. Finally, recent data have identified a subset of follicular T helper cells dependent on IL-13 which selectively trigger massive IgE accumulation in response to anaphylactoid allergens. Thus, prophylactic IL-13 vaccination may have broad application in a number of allergic conditions. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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16 pages, 1057 KiB

Open AccessReview

Recent Advances in the Use of Plant Virus-Like Particles as Vaccines

by Ina Balke and Andris Zeltins

Viruses 2020, 12(3), 270; https://doi.org/10.3390/v12030270 - 28 Feb 2020

Cited by 41 | Viewed by 8719

Abstract

Vaccination is one of the most effective public health interventions of the 20th century. All vaccines can be classified into different types, such as vaccines against infectious diseases, anticancer vaccines and vaccines against autoimmune diseases. In recent decades, recombinant technologies have enabled the [...] Read more.

Vaccination is one of the most effective public health interventions of the 20th century. All vaccines can be classified into different types, such as vaccines against infectious diseases, anticancer vaccines and vaccines against autoimmune diseases. In recent decades, recombinant technologies have enabled the design of experimental vaccines against a wide range of diseases using plant viruses and virus-like particles as central elements to stimulate protective and long-lasting immune responses. The analysis of recent publications shows that at least 97 experimental vaccines have been constructed based on plant viruses, including 71 vaccines against infectious agents, 16 anticancer vaccines and 10 therapeutic vaccines against autoimmune disorders. Several plant viruses have already been used for the development of vaccine platforms and have been tested in human and veterinary studies, suggesting that plant virus-based vaccines will be introduced into clinical and veterinary practice in the near future. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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14 pages, 329 KiB

Open AccessReview

Advantages and Prospects of Tag/Catcher Mediated Antigen Display on Capsid-Like Particle-Based Vaccines

by Kara-Lee Aves, Louise Goksøyr and Adam F. Sander

Viruses 2020, 12(2), 185; https://doi.org/10.3390/v12020185 - 06 Feb 2020

Cited by 18 | Viewed by 3928

Abstract

Capsid-like particles (CLPs) are multimeric, repetitive assemblies of recombinant viral capsid proteins, which are highly immunogenic due to their structural similarity to wild-type viruses. CLPs can be used as molecular scaffolds to enable the presentation of soluble vaccine antigens in a similar structural [...] Read more.

Capsid-like particles (CLPs) are multimeric, repetitive assemblies of recombinant viral capsid proteins, which are highly immunogenic due to their structural similarity to wild-type viruses. CLPs can be used as molecular scaffolds to enable the presentation of soluble vaccine antigens in a similar structural format, which can significantly increase the immunogenicity of the antigen. CLP-based antigen display can be obtained by various genetic and modular conjugation methods. However, these vary in their versatility as well as efficiency in achieving an immunogenic antigen display. Here, we make a comparative review of the major CLP-based antigen display technologies. The Tag/Catcher-AP205 platform is highlighted as a particularly versatile and efficient technology that offers new qualitative and practical advantages in designing modular CLP vaccines. Finally, we discuss how split-protein Tag/Catcher conjugation systems can help to further propagate and enhance modular CLP vaccine designs. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

26 pages, 1880 KiB

Open AccessReview

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

by Joan Kha-Tu Ho, Beena Jeevan-Raj and Hans-Jürgen Netter

Viruses 2020, 12(2), 126; https://doi.org/10.3390/v12020126 - 21 Jan 2020

Cited by 63 | Viewed by 11437

Abstract

Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed [...] Read more.

Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed of the HBV surface (envelope) protein (HBsAg) to reduce the risk of new infections. The isolation of HBsAg sub-viral particles (SVPs) from the blood of asymptomatic HBV carriers as antigens for the first-generation vaccines, followed by the development of recombinant HBsAg SVPs produced in yeast as the antigenic components of the second-generation vaccines, represent landmark advancements in biotechnology and medicine. The ability of the HBsAg SVPs to accept and present foreign antigenic sequences provides the basis of a chimeric particulate delivery platform, and resulted in the development of a vaccine against malaria (RTS,S/AS01, Mosquirix^TM), and various preclinical vaccine candidates to overcome infectious diseases for which there are no effective vaccines. Biomedical modifications of the HBsAg subunits allowed the identification of strategies to enhance the HBsAg SVP immunogenicity to build potent vaccines for preventative and possibly therapeutic applications. The review provides an overview of the formation and assembly of the HBsAg SVPs and highlights the utilization of the particles in key effective vaccines. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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15 pages, 796 KiB

Open AccessReview

Prophylactic Hepatitis E Vaccines: Antigenic Analysis and Serological Evaluation

by Yike Li, Xiaofen Huang, Zhigang Zhang, Shaowei Li, Jun Zhang, Ningshao Xia and Qinjian Zhao

Viruses 2020, 12(1), 109; https://doi.org/10.3390/v12010109 - 16 Jan 2020

Cited by 15 | Viewed by 4737

Abstract

Hepatitis E virus (HEV) infection causes sporadic outbreaks of acute hepatitis worldwide. HEV was previously considered to be restricted to resource-limited countries with poor sanitary conditions, but increasing evidence implies that HEV is also a public health problem in developed countries and regions. [...] Read more.

Hepatitis E virus (HEV) infection causes sporadic outbreaks of acute hepatitis worldwide. HEV was previously considered to be restricted to resource-limited countries with poor sanitary conditions, but increasing evidence implies that HEV is also a public health problem in developed countries and regions. Fortunately, several vaccine candidates based on virus-like particles (VLPs) have progressed into the clinical development stage, and one of them has been approved in China. This review provides an overview of the current HEV vaccine pipeline and future development with the emphasis on defining the critical quality attributes for the well-characterized vaccines. The presence of clinically relevant epitopes on the VLP surface is critical for eliciting functional antibodies against HEV infection, which is the key to the mechanism of action of the prophylactic vaccines against viral infections. Therefore, the epitope-specific immunochemical assays based on monoclonal antibodies (mAbs) for HEV vaccine antigen are critical methods in the toolbox for epitope characterization and for in vitro potency assessment. Moreover, serological evaluation methods after immunization are also discussed as biomarkers for clinical performance. The vaccine efficacy surrogate assays are critical in the preclinical and clinical stages of VLP-based vaccine development. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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10 pages, 1525 KiB

Open AccessReview

Factors That Govern the Induction of Long-Lived Antibody Responses

by Bryce Chackerian and David S. Peabody

Viruses 2020, 12(1), 74; https://doi.org/10.3390/v12010074 - 07 Jan 2020

Cited by 22 | Viewed by 4480

Abstract

The induction of long-lasting, high-titer antibody responses is critical to the efficacy of many vaccines. The ability to produce durable antibody responses is governed by the generation of the terminally differentiated antibody-secreting B cells known as long-lived plasma cells (LLPCs). Once induced, LLPCs [...] Read more.

The induction of long-lasting, high-titer antibody responses is critical to the efficacy of many vaccines. The ability to produce durable antibody responses is governed by the generation of the terminally differentiated antibody-secreting B cells known as long-lived plasma cells (LLPCs). Once induced, LLPCs likely persist for decades, providing long-term protection against infection. The factors that control the generation of this important class of B cells are beginning to emerge. In particular, antigens with highly dense, multivalent structures are especially effective. Here we describe some pathogens for which the induction of long-lived antibodies is particularly important, and discuss the basis for the extraordinary ability of multivalent antigens to drive differentiation of naïve B cells to LLPCs. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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17 pages, 2455 KiB

Open AccessReview

Virus-Like Particles and Nanoparticles for Vaccine Development against HCMV

by Michela Perotti and Laurent Perez

Viruses 2020, 12(1), 35; https://doi.org/10.3390/v12010035 - 28 Dec 2019

Cited by 24 | Viewed by 7796

Abstract

Human cytomegalovirus (HCMV) infects more than 70% of the human population worldwide. HCMV is responsible for high morbidity and mortality in immunocompromised patients and remains the leading viral cause of congenital birth defects. Despite considerable efforts in vaccine and therapeutic development, HCMV infection [...] Read more.

Human cytomegalovirus (HCMV) infects more than 70% of the human population worldwide. HCMV is responsible for high morbidity and mortality in immunocompromised patients and remains the leading viral cause of congenital birth defects. Despite considerable efforts in vaccine and therapeutic development, HCMV infection still represents an unmet clinical need and a life-threatening disease in immunocompromised individuals and newborns. Immune repertoire interrogation of HCMV seropositive patients allowed the identification of several potential antigens for vaccine design. However, recent HCMV vaccine clinical trials did not lead to a satisfactory outcome in term of efficacy. Therefore, combining antigens with orthogonal technologies to further increase the induction of neutralizing antibodies could improve the likelihood of a vaccine to reach protective efficacy in humans. Indeed, presentation of multiple copies of an antigen in a repetitive array is known to drive a more robust humoral immune response than its soluble counterpart. Virus-like particles (VLPs) and nanoparticles (NPs) are powerful platforms for multivalent antigen presentation. Several self-assembling proteins have been successfully used as scaffolds to present complex glycoprotein antigens on their surface. In this review, we describe some key aspects of the immune response to HCMV and discuss the scaffolds that were successfully used to increase vaccine efficacy against viruses with unmet medical need. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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17 pages, 2645 KiB

Open AccessReview

Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

by Rashi Yadav, Lukai Zhai and Ebenezer Tumban

Viruses 2020, 12(1), 18; https://doi.org/10.3390/v12010018 - 23 Dec 2019

Cited by 31 | Viewed by 7426

Abstract

Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and [...] Read more.

Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further. Full article

(This article belongs to the Special Issue Virus-Like Particle Vaccines)

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