The Immune Correlates of Orthohantavirus Vaccine

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due to the relative paucity of cases in countries outside China and Korea. However, the orthohantaviruses continuously evolve in hosts and thus the current vaccine may not work as well against some variants. Therefore, a more effective vaccine should be prepared against the orthohantaviruses. In this review, we discuss the issues caused by the orthohantavirus vaccine. Given the pros and cons of the orthohantavirus vaccine, we suggest strategies for the development of better vaccines in terms of pandemic preparedness.

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Coronavirus vaccine development: from SARS and MERS to COVID-19

Journal of Biomedical Science ◽

10.1186/s12929-020-00695-2 ◽

2020 ◽

Vol 27 (1) ◽

Author(s):

Yen-Der Li ◽

Wei-Yu Chi ◽

Jun-Han Su ◽

Louise Ferrall ◽

Chien-Fu Hung ◽

...

Keyword(s):

Middle East ◽

Severe Acute Respiratory Syndrome ◽

High Mortality ◽

Recent Progress ◽

Vaccine Development ◽

Middle East Respiratory Syndrome ◽

Effective Vaccine ◽

Rapid Spread ◽

New Type ◽

Pros And Cons

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development.

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Tuberculosis Vaccine Development: Progress in Clinical Evaluation

Clinical Microbiology Reviews ◽

10.1128/cmr.00100-19 ◽

2019 ◽

Vol 33 (1) ◽

Cited By ~ 16

Author(s):

Suraj B. Sable ◽

James E. Posey ◽

Thomas J. Scriba

Keyword(s):

Clinical Trials ◽

Clinical Evaluation ◽

Vaccine Development ◽

Effective Vaccine ◽

Natural Immunity ◽

Content Type ◽

Vaccine Candidates ◽

Current Vaccine ◽

Development Trajectory ◽

Airborne Disease

SUMMARY Tuberculosis (TB) is the leading killer among all infectious diseases worldwide despite extensive use of the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine. A safer and more effective vaccine than BCG is urgently required. More than a dozen TB vaccine candidates are under active evaluation in clinical trials aimed to prevent infection, disease, and recurrence. After decades of extensive research, renewed promise of an effective vaccine against this ancient airborne disease has recently emerged. In two innovative phase 2b vaccine clinical trials, one for the prevention of Mycobacterium tuberculosis infection in healthy adolescents and another for the prevention of TB disease in M. tuberculosis-infected adults, efficacy signals were observed. These breakthroughs, based on the greatly expanded knowledge of the M. tuberculosis infection spectrum, immunology of TB, and vaccine platforms, have reinvigorated the TB vaccine field. Here, we review our current understanding of natural immunity to TB, limitations in BCG immunity that are guiding vaccinologists to design novel TB vaccine candidates and concepts, and the desired attributes of a modern TB vaccine. We provide an overview of the progress of TB vaccine candidates in clinical evaluation, perspectives on the challenges faced by current vaccine concepts, and potential avenues to build on recent successes and accelerate the TB vaccine research-and-development trajectory.

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Differential Immune Response Following Intranasal and Intradermal Infection with Francisella tularensis: Implications for Vaccine Development

Microorganisms ◽

10.3390/microorganisms9050973 ◽

2021 ◽

Vol 9 (5) ◽

pp. 973

Author(s):

McKayla J. Nicol ◽

David R. Williamson ◽

David E. Place ◽

Girish S. Kirimanjeswara

Keyword(s):

Francisella Tularensis ◽

Vaccine Development ◽

Natural Infection ◽

Effective Vaccine ◽

Adaptive Immune ◽

Immune Correlates ◽

Disease Outcomes ◽

Clinical Presentations ◽

Clinical Diagnoses ◽

Disease Understanding

Francisella tularensis (Ft) is a Gram-negative, facultative intracellular coccobacillus that is the etiological agent of tularemia. Interestingly, the disease tularemia has variable clinical presentations that are dependent upon the route of infection with Ft. Two of the most likely routes of Ft infection include intranasal and intradermal, which result in pneumonic and ulceroglandular tularemia, respectively. While there are several differences between these two forms of tularemia, the most notable disparity is between mortality rates: the mortality rate following pneumonic tularemia is over ten times that of the ulceroglandular disease. Understanding the differences between intradermal and intranasal Ft infections is important not only for clinical diagnoses and treatment but also for the development of a safe and effective vaccine. However, the immune correlates of protection against Ft, especially within the context of infection by disparate routes, are not yet fully understood. Recent advances in different animal models have revealed new insights in the complex interplay of innate and adaptive immune responses, indicating dissimilar patterns in both responses following infection with Ft via different routes. Further investigation of these differences will be crucial to predicting disease outcomes and inducing protective immunity via vaccination or natural infection.

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Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽

10.3390/pharmaceutics13020140 ◽

2021 ◽

Vol 13 (2) ◽

pp. 140

Author(s):

Abdellatif Bouazzaoui ◽

Ahmed A. H. Abdellatif ◽

Faisal A. Al-Allaf ◽

Neda M. Bogari ◽

Saied Al-Dehlawi ◽

...

Keyword(s):

Viral Vectors ◽

Protein Production ◽

Vaccine Development ◽

Effective Vaccine ◽

The Novel ◽

Research Teams ◽

Advantages And Disadvantages ◽

Rapid Spread ◽

New Generation ◽

Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

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SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽

10.1038/s41541-021-00292-w ◽

2021 ◽

Vol 6 (1) ◽

Cited By ~ 3

Author(s):

Nikolaos C. Kyriakidis ◽

Andrés López-Cortés ◽

Eduardo Vásconez González ◽

Alejandra Barreto Grimaldos ◽

Esteban Ortiz Prado

Keyword(s):

Neutralizing Antibodies ◽

Large Scale ◽

Vaccine Development ◽

Rna Virus ◽

Protein S ◽

Effective Vaccine ◽

Phase 3 ◽

Vaccine Candidates ◽

Advantages And Disadvantages ◽

The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

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Intention to Be Vaccinated for COVID-19 among Italian Nurses during the Pandemic

Vaccines ◽

10.3390/vaccines9050500 ◽

2021 ◽

Vol 9 (5) ◽

pp. 500

Author(s):

Marco Trabucco Aurilio ◽

Francesco Saverio Mennini ◽

Simone Gazzillo ◽

Laura Massini ◽

Matteo Bolcato ◽

...

Keyword(s):

Vaccine Efficacy ◽

Online Survey ◽

Vaccine Development ◽

Vaccine Coverage ◽

World Health ◽

Vaccine Hesitancy ◽

Effective Vaccine ◽

Online Questionnaire ◽

Cross Sectional ◽

Female Sex

Background: While the COVID-19 pandemic has spread globally, health systems are overwhelmed by both direct and indirect mortality from other treatable conditions. COVID-19 vaccination was crucial to preventing and eliminating the disease, so vaccine development for COVID-19 was fast-tracked worldwide. Despite the fact that vaccination is commonly recognized as the most effective approach, according to the World Health Organization (WHO), vaccine hesitancy is a global health issue. Methods: We conducted a cross-sectional online survey of nurses in four different regions in Italy between 20 and 28 December 2020 to obtain data on the acceptance of the upcoming COVID-19 vaccination in order to plan specific interventions to increase the rate of vaccine coverage. Results: A total of 531 out of the 5000 nurses invited completed the online questionnaire. Most of the nurses enrolled in the study (73.4%) were female. Among the nurses, 91.5% intended to accept vaccination, whereas 2.3% were opposed and 6.2% were undecided. Female sex and confidence in vaccine efficacy represent the main predictors of vaccine intention among the study population using a logistic regression model, while other factors including vaccine safety concerns (side effects) were non-significant. Conclusions: Despite the availability of a safe and effective vaccine, intention to be vaccinated was suboptimal among nurses in our sample. We also found a significant number of people undecided as to whether to accept the vaccine. Contrary to expectations, concerns about the safety of the vaccine were not found to affect the acceptance rate; nurses’ perception of vaccine efficacy and female sex were the main influencing factors on attitudes toward vaccination in our sample. Since the success of the COVID-19 immunization plan depends on the uptake rate, these findings are of great interest for public health policies. Interventions aimed at increasing employee awareness of vaccination efficacy should be promoted among nurses in order to increase the number of vaccinated people.

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A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00588-2 ◽

2021 ◽

Author(s):

Vincent Legros ◽

Solène Denolly ◽

Manon Vogrig ◽

Bertrand Boson ◽

Eglantine Siret ◽

...

Keyword(s):

Intensive Care ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Surface Protein ◽

Humoral Response ◽

Neutralizing Antibody ◽

Rapid Decline ◽

Serum Samples ◽

Immune Correlates ◽

Human Coronaviruses

AbstractUnderstanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

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COVID-19: Mechanisms of Vaccination and Immunity

Vaccines ◽

10.3390/vaccines8030404 ◽

2020 ◽

Vol 8 (3) ◽

pp. 404 ◽

Cited By ~ 1

Author(s):

Daniel E. Speiser ◽

Martin F. Bachmann

Keyword(s):

Immune Responses ◽

Clinical Management ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Public Life ◽

High Affinity ◽

Vaccination Strategies ◽

Detailed Evaluation ◽

Pros And Cons

Vaccines are needed to protect from SARS-CoV-2, the virus causing COVID-19. Vaccines that induce large quantities of high affinity virus-neutralizing antibodies may optimally prevent infection and avoid unfavorable effects. Vaccination trials require precise clinical management, complemented with detailed evaluation of safety and immune responses. Here, we review the pros and cons of available vaccine platforms and options to accelerate vaccine development towards the safe immunization of the world’s population against SARS-CoV-2. Favorable vaccines, used in well-designed vaccination strategies, may be critical for limiting harm and promoting trust and a long-term return to normal public life and economy.

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Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽

10.3390/vaccines8020302 ◽

2020 ◽

Vol 8 (2) ◽

pp. 302 ◽

Cited By ~ 1

Author(s):

Anthony C. Ike ◽

Chisom J. Onu ◽

Chukwuebuka M. Ononugbo ◽

Eleazar E. Reward ◽

Sophia O. Muo

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Viral Infections ◽

Recombinant Dna ◽

Vaccine Development ◽

The Body ◽

Effective Vaccine ◽

Subunit Vaccines ◽

Simplex Virus ◽

Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

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A GMMA-CPS-Based Vaccine for Non-Typhoidal Salmonella

Vaccines ◽

10.3390/vaccines9020165 ◽

2021 ◽

Vol 9 (2) ◽

pp. 165

Author(s):

Akosiererem S. Sokaribo ◽

Sumudu R. Perera ◽

Zoe Sereggela ◽

Ryan Krochak ◽

Lindsay R. Balezantis ◽

...

Keyword(s):

Vaccine Development ◽

Random Mutagenesis ◽

Bloodstream Infections ◽

Sub Saharan Africa ◽

Colanic Acid ◽

High Fatality Rate ◽

Current Vaccine ◽

Membrane Antigens ◽

Human Use ◽

Sub Saharan

Non-typhoidal Salmonella are a major cause of gastroenteritis worldwide, as well as causing bloodstream infections in sub-Saharan Africa with a high fatality rate. No vaccine is currently available for human use. Current vaccine development strategies are focused on capsular polysaccharides (CPS) present on the surface of non-typhoidal Salmonella. This study aimed to boost the amount of CPS purified from S. Typhimurium for immunization trials. Random mutagenesis with Tn10 transposon increased the production of CPS colanic acid, by 10-fold compared to wildtype. Immunization with colanic acid or colanic acid conjugated to truncated glycoprotein D or inactivated diphtheria toxin did not induce a protective immune response in mice. However, immunization with Generalized Modules for Membrane Antigens (GMMAs) isolated from colanic acid overproducing isolates reduced Salmonella colonization in mice. Our results support the development of a GMMA-CPS-based vaccine against non-typhoidal Salmonella.

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