How to Increase the Immunogenicity of SARS-COV-2 Inactivated Vaccines?

To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide. The earliest vaccines were developed as live-attenuated or inactivated pathogens, and, although they still represent the most extended human vaccine types, they also face some issues, such as the potential to revert to a pathogenic form of live-attenuated formulations or the weaker immune response associated with inactivated vaccines. Advances in genetic engineering have enabled improvements in vaccine design and strategies, such as recombinant subunit vaccines, have emerged, expanding the number of diseases that can be prevented. Moreover, antigen display systems such as VLPs or those designed by nanotechnology have improved the efficacy of subunit vaccines. Platforms for the production of recombinant vaccines have also evolved from the first hosts, Escherichia coli and Saccharomyces cerevisiae, to insect or mammalian cells. Traditional bacterial and yeast systems have been improved by engineering and new systems based on plants or insect larvae have emerged as alternative, low-cost platforms. Vaccine development is still time-consuming and costly, and alternative systems that can offer cost-effective and faster processes are demanding to address infectious diseases that still do not have a treatment and to face possible future pandemics.

Download Full-text

Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

Medical Sciences ◽

10.3390/medsci9030053 ◽

2021 ◽

Vol 9 (3) ◽

pp. 53

Author(s):

Giuseppe Tardiolo ◽

Pina Brianti ◽

Daniela Sapienza ◽

Pia dell’Utri ◽

Viviane Di Dio ◽

...

Keyword(s):

Animal Models ◽

Viral Vector ◽

Herd Immunity ◽

Population Level ◽

Narrative Review ◽

Therapeutic Interventions ◽

Preclinical Research ◽

Inactivated Vaccines ◽

Preclinical And Clinical Studies ◽

Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

Download Full-text

Animal Models and Alternatives in the Quality Control of Vaccines: Are In Vitro Methods or In Vivo Methods the Scientific Equivalent of the Emperor's New Clothes?

Alternatives to Laboratory Animals ◽

10.1177/026119299502300110 ◽

1995 ◽

Vol 23 (1) ◽

pp. 61-73

Author(s):

Coenraad Hendriksen ◽

Johan van der Gun

Keyword(s):

Quality Control ◽

Test Methods ◽

In Vitro Test ◽

Large Numbers ◽

Alternative Approach ◽

Inactivated Vaccines ◽

Vitro Test

In the quality control of vaccine batches, the potency testing of inactivated vaccines is one of the areas requiring very large numbers of animals, which usually suffer significant distress as a result of the experimental procedures employed. This article deals with the potency testing of diphtheria and tetanus toxoids, two vaccines which are used extensively throughout the world. The relevance of the potency test prescribed by the European Pharmacopoeia monographs is questioned. The validity of the potency test as a model for the human response, the ability of the test to be standardised, and the relevance of the test in relation to the quality of the product are discussed. It is concluded that the potency test has only limited predictive value for the antitoxin responses to be expected in recipients of these toxoids. An alternative approach for estimating the potency of toxoid batches is discussed, in which a distinction is made between estimation of the immunogenic potency of the first few batches obtained from a seed lot and monitoring the consistency of the quality of subsequent batches. The use of animals is limited to the first few batches. Monitoring the consistency of the quality of subsequent batches is based on in vitro test methods. Factors which hamper the introduction and acceptance of the alternative approach are considered. Finally, proposals are made for replacement, reduction and/or refinement (the Three Rs) in the use of animals in the routine potency testing of toxoids.

Download Full-text

Development of a Safe and Highly Efficient Inactivated Vaccine Candidate against Lumpy Skin Disease Virus

Vaccines ◽

10.3390/vaccines9010004 ◽

2020 ◽

Vol 9 (1) ◽

pp. 4

Author(s):

Janika Wolff ◽

Tom Moritz ◽

Kore Schlottau ◽

Donata Hoffmann ◽

Martin Beer ◽

...

Keyword(s):

Skin Disease ◽

Animal Health ◽

Vaccine Virus ◽

Lumpy Skin Disease ◽

Virus Shedding ◽

Clinical Protection ◽

Inactivated Vaccines ◽

Disease Free ◽

World Organisation ◽

Free Status

Capripox virus (CaPV)-induced diseases (lumpy skin disease, sheeppox, goatpox) are described as the most serious pox diseases of livestock animals, and therefore are listed as notifiable diseases under guidelines of the World Organisation for Animal Health (OIE). Until now, only live-attenuated vaccines are commercially available for the control of CaPV. Due to numerous potential problems after vaccination (e.g., loss of the disease-free status of the respective country, the possibility of vaccine virus shedding and transmission as well as the risk of recombination with field strains during natural outbreaks), the use of these vaccines must be considered carefully and is not recommended in CaPV-free countries. Therefore, innocuous and efficacious inactivated vaccines against CaPV would provide a great tool for control of these diseases. Unfortunately, most inactivated Capripox vaccines were reported as insufficient and protection seemed to be only short-lived. Nevertheless, a few studies dealing with inactivated vaccines against CaPV are published, giving evidence for good clinical protection against CaPV-infections. In our studies, a low molecular weight copolymer-adjuvanted vaccine formulation was able to induce sterile immunity in the respective animals after severe challenge infection. Our findings strongly support the possibility of useful inactivated vaccines against CaPV-infections, and indicate a marked impact of the chosen adjuvant for the level of protection.

Download Full-text

The efficacy of live and inactivated vaccines of Hong Kong influenza virus in an industrial community: A report to the Medical Research Council Committee on Influenza and other respiratory virus vaccines

Epidemiology and Infection ◽

10.1017/s0022172400022907 ◽

1973 ◽

Vol 71 (4) ◽

pp. 641-647 ◽

Cited By ~ 14

Author(s):

D. Hobson ◽

F. A. Baker ◽

R. L. Curry ◽

A. S. Beare ◽

P. M. O. Massey

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Medical Research ◽

Research Council ◽

Respiratory Virus ◽

Medical Research Council ◽

Influenza Viruses ◽

Protective Efficiency ◽

Industrial Community ◽

Inactivated Vaccines

Intranasal vaccines of inactivated or living attentuated A2/Hong Kong influenza viruses were compared for clinical acceptability, serological effects and protective efficiency against natural epidemic influenza in a large industrial and clerical population.

Download Full-text

Towards Improved Use of Vaccination in the Control of Infectious Bronchitis and Newcastle Disease in Poultry: Understanding the Immunological Mechanisms

Vaccines ◽

10.3390/vaccines9010020 ◽

2021 ◽

Vol 9 (1) ◽

pp. 20

Author(s):

Anthony C. Ike ◽

Chukwuebuka M. Ononugbo ◽

Okechukwu J. Obi ◽

Chisom J. Onu ◽

Chinasa V. Olovo ◽

...

Keyword(s):

Immune Responses ◽

Newcastle Disease ◽

Viral Infections ◽

Advanced Technology ◽

Global Food Security ◽

Infectious Bronchitis ◽

Immunological Mechanisms ◽

Inactivated Vaccines ◽

Successful Control ◽

Cellular Immune

Infectious bronchitis (IB) and Newcastle disease (ND) are two important diseases of poultry and have remained a threat to the development of the poultry industry in many parts of the world. The immunology of avian has been well studied and numerous vaccines have been developed against the two viruses. Most of these vaccines are either inactivated vaccines or live attenuated vaccines. Inactivated vaccines induce weak cellular immune responses and require priming with live or other types of vaccines. Advanced technology has been used to produce several types of vaccines that can initiate prime immune responses. However, as a result of rapid genetic variations, the control of these two viral infections through vaccination has remained a challenge. Using various strategies such as combination of live attenuated and inactivated vaccines, development of IB/ND vaccines, use of DNA vaccines and transgenic plant vaccines, the problem is being surmounted. It is hoped that with increasing understanding of the immunological mechanisms in birds that are used in fighting these viruses, a more successful control of the diseases will be achieved. This will go a long way in contributing to global food security and the economic development of many developing countries, given the role of poultry in the attainment of these goals.

Download Full-text

Current Status of Zika Virus Vaccines: Successes and Challenges

Vaccines ◽

10.3390/vaccines8020266 ◽

2020 ◽

Vol 8 (2) ◽

pp. 266 ◽

Cited By ~ 6

Author(s):

Aryamav Pattnaik ◽

Bikash R. Sahoo ◽

Asit K. Pattnaik

Keyword(s):

Zika Virus ◽

Viral Infections ◽

Current Status ◽

Effective Vaccine ◽

Congenital Diseases ◽

Vaccine Candidates ◽

Efficacy Trials ◽

Nucleic Acid Vaccines ◽

Funding Agencies ◽

Inactivated Vaccines

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs.

Download Full-text

Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

Vaccines ◽

10.3390/vaccines9050480 ◽

2021 ◽

Vol 9 (5) ◽

pp. 480

Author(s):

Honglei Wang ◽

Yangyang Xu ◽

Wenhai Feng

Keyword(s):

Immune Responses ◽

Reverse Genetics ◽

Vaccine Development ◽

Immune Escape ◽

Rna Virus ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Live Vaccines ◽

Host Immune Responses ◽

Inactivated Vaccines

Porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus widely prevalent in pigs, results in significant economic losses worldwide. PRRSV can escape from the host immune response in several processes. Vaccines, including modified live vaccines and inactivated vaccines, are the best available countermeasures against PRRSV infection. However, challenges still exist as the vaccines are not able to induce broad protection. The reason lies in several facts, mainly the variability of PRRSV and the complexity of the interaction between PRRSV and host immune responses, and overcoming these obstacles will require more exploration. Many novel strategies have been proposed to construct more effective vaccines against this evolving and smart virus. In this review, we will describe the mechanisms of how PRRSV induces weak and delayed immune responses, the current vaccines of PRRSV, and the strategies to develop modified live vaccines using reverse genetics systems.

Download Full-text