scholarly journals Comparative analysis of existing platforms for the development of vaccines against dangerous and extremely dangerous viral infections with pandemic potential

2021 ◽  
Vol 21 (4) ◽  
pp. 225-233
Author(s):  
G. G. Onishchenko ◽  
T. E. Sizikova ◽  
V. N. Lebedev ◽  
S. V. Borisevich

The main triggers of new infectious diseases, including those with pandemic potential, are: spontaneous emergence of infectious strains which are more virulent for humans and contribute to transmission of pathogenic microorganisms, environmental changes, social and economic factors, increased contact rates between different regions. A successful pandemic response requires mass immunisation against a specific disease, aimed at the development of herd immunity which is based on the concept of indirect protection of the whole of the population by immunising a part of it. A well-grounded choice of the vaccine platform is central to dealing with this problem. The aim of the study was to compare characteristics of vaccine platforms (attenuated, inactivated, subunit, recombinant vector, DNA, and RNA vaccines) intended for mass immunisation against dangerous and extremely dangerous viral infections with pandemic potential. The study focused on the members of Poxviridae, Orthomyxoviridae and Coronaviridae families as potential pathogens. The vaccine platforms were compared in terms of the following parameters: capability of producing a robust immune response; protective efficacy; time required for vaccine development and testing; ability to produce vaccine in volumes required for mass immunisation; potential obstacles associated with the intended use of the vaccine. It is expected that in the next few decades DNA and RNA vaccine platforms will be most widely used for development of products against dangerous and extremely dangerous viral infections with pandemic potential, regardless of taxonomic groups of pathogens.

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Pratibha Anand ◽  
Vincent P. Stahel

AbstractThe novel coronavirus disease 2019 (COVID-19) has infected more than 100 million people globally within the first year of the pandemic. With a death toll surpassing 500,000 in the United States alone, containing the pandemic is predicated on achieving herd immunity on a global scale. This implies that at least 70-80 % of the population must achieve active immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), either as a result of a previous COVID-19 infection or by vaccination against SARS-CoV-2. In December 2020, the first two vaccines were approved by the FDA through emergency use authorization in the United States. These vaccines are based on the mRNA vaccine platform and were developed by Pfizer/BioNTech and Moderna. Published safety and efficacy trials reported high efficacy rates of 94-95 % after two interval doses, in conjunction with limited side effects and a low rate of adverse reactions. The rapid pace of vaccine development and the uncertainty of potential long-term adverse effects raised some level of hesitation against mRNA vaccines in the global community. A successful vaccination campaign is contingent on widespread access to the vaccine under appropriate storage conditions, deployment of a sufficient number of vaccinators, and the willingness of the population to be vaccinated. Thus, it is important to clarify the objective data related to vaccine safety, including known side effects and potential adverse reactions. The present review was designed to provide an update on the current state of science related to the safety and efficacy of SARS-CoV-2 mRNA vaccines.


2021 ◽  
Vol 14 (5) ◽  
pp. 406
Author(s):  
Zhi-Peng Yan ◽  
Ming Yang ◽  
Ching-Lung Lai

Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations.


2020 ◽  
Vol 20 (4) ◽  
pp. 216-227
Author(s):  
G. G. Onishchenko ◽  
T. E. Sizikova ◽  
V. N. Lebedev ◽  
S. V. Borisevich

The number of confirmed COVID-19 cases worldwide amounted to 50 million at the beginning of November 2020. This is clearly not enough for the formation of herd immunity, which will prevent repeated outbreaks of the disease. Quarantine measures can only curb the spread of the disease to some extent, therefore specific preventive measures are needed to create collective immunity to COVID-19.The underlying principle of collective immunity is indirect protection of the whole of the population by immunising a certain part of it. Vaccination is the most effective approach to prevention of epidemic outbreaks. The aim of the study was to analyse promising approaches to the development of vaccines against novel coronavirus COVID-19 infection. The paper summarises data on development studies and clinical trials of COVID-19 vaccines conducted in different countries. It analyses the pros and cons of different platforms for vaccine development (attenuated vaccines, inactivated vaccines, subunit vaccines, DNA and RNA vaccines, recombinant vector vaccines). The paper presents a potential design of novel vaccines. It was concluded that COVID-19 vaccines might be developed both for immunising high-risk groups and for mass immunisation. An optimal solution for the second task would be to develop human or monkey adenovirus vector-based vaccines whose mass production has already been unveiled.


2020 ◽  
Author(s):  
Laura Lafon-Hughes

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.


2020 ◽  
Vol 11 ◽  
Author(s):  
Lea Skak Filtenborg Frederiksen ◽  
Yibang Zhang ◽  
Camilla Foged ◽  
Aneesh Thakur

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 302 ◽  
Author(s):  
Anthony C. Ike ◽  
Chisom J. Onu ◽  
Chukwuebuka M. Ononugbo ◽  
Eleazar E. Reward ◽  
Sophia O. Muo

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.


2021 ◽  
Author(s):  
Jin Gao ◽  
Laura Klenow ◽  
Lisa Parsons ◽  
Tahir Malik ◽  
Je-Nie Phue ◽  
...  

Supplementing influenza vaccines with recombinant neuraminidase (rNA) antigens remains a promising approach for improving the suboptimal vaccine efficacy. However, correlations among rNA designs, properties, and protection have not been systematically investigated. Here, we performed a comparative analysis of several rNAs produced using the baculovirus/insect cell system. The rNAs were designed with different tetramerization motifs and NA domains from a recent H1N1 vaccine strain (A/Brisbane/02/2018) and were compared for enzymatic property, antigenicity, stability, and protection in mice. We found that distinct enzymatic properties are associated with rNAs containing the NA head-domain versus the full-ectodomain, formation of higher order rNA oligomers is tetramerization domain-dependent, whereas protective efficacy is more contingent on the combination of the tetramerization and NA domains. Following single-dose immunizations, a rNA possessing the full-ectodomain and the tetramerization motif from the human vasodilator-stimulated phosphoprotein provided much better protection than a rNA with ∼10-fold more enzymatically active molecules that is comprised of the head-domain and the same tetramerization motif. In contrast, these two rNA designs provided comparable protection when the tetramerization motif from the tetrabrachion protein was used instead. These findings demonstrate that individual rNAs should be thoroughly evaluated for vaccine development, as the heterologous domain combination can result in rNAs with similar key attributes but vastly differ in protection. IMPORTANCE For several decades it has been proposed that influenza vaccines could be supplemented with recombinant neuraminidase (rNA) to improve the efficacy. However, some key questions for manufacturing stable and immunogenic rNA remain to be answered. We show here that the tetramerization motifs and NA domains included in the rNA construct design can have a profound impact on the biochemical, immunogenic and protective properties. We also show that the single-dose immunization regimen is more informative for assessing the rNA immune response and protective efficacy, which is surprisingly more dependent on the specific combination of NA and tetramerization domains than common attributes for evaluating NA. Our findings may help to optimize the design of rNAs that can be used to improve or develop influenza vaccines.


2021 ◽  
Vol 13 (583) ◽  
pp. eabe5449
Author(s):  
Nicole Darricarrère ◽  
Yu Qiu ◽  
Masaru Kanekiyo ◽  
Adrian Creanga ◽  
Rebecca A. Gillespie ◽  
...  

Seasonal influenza vaccines confer protection against specific viral strains but have restricted breadth that limits their protective efficacy. The H1 and H3 subtypes of influenza A virus cause most of the seasonal epidemics observed in humans and are the major drivers of influenza A virus–associated mortality. The consequences of pandemic spread of COVID-19 underscore the public health importance of prospective vaccine development. Here, we show that headless hemagglutinin (HA) stabilized-stem immunogens presented on ferritin nanoparticles elicit broadly neutralizing antibody (bnAb) responses to diverse H1 and H3 viruses in nonhuman primates (NHPs) when delivered with a squalene-based oil-in-water emulsion adjuvant, AF03. The neutralization potency and breadth of antibodies isolated from NHPs were comparable to human bnAbs and extended to mismatched heterosubtypic influenza viruses. Although NHPs lack the immunoglobulin germline VH1-69 residues associated with the most prevalent human stem-directed bnAbs, other gene families compensated to generate bnAbs. Isolation and structural analyses of vaccine-induced bnAbs revealed extensive interaction with the fusion peptide on the HA stem, which is essential for viral entry. Antibodies elicited by these headless HA stabilized-stem vaccines neutralized diverse H1 and H3 influenza viruses and shared a mode of recognition analogous to human bnAbs, suggesting that these vaccines have the potential to confer broadly protective immunity against diverse viruses responsible for seasonal and pandemic influenza infections in humans.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2443 ◽  
Author(s):  
Zi Li ◽  
Wenqi He ◽  
Yungang Lan ◽  
Kui Zhao ◽  
Xiaoling Lv ◽  
...  

An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.


1991 ◽  
Vol 4 (3) ◽  
pp. 499 ◽  
Author(s):  
GI Jordan ◽  
RS Hill

Subtribe Banksiinae of the Proteaceae was diverse in Tasmania in the early and middle Tertiary, but is now restricted to two species, Banksia marginata and B. serrata. Rapid and extreme environmental changes during the Pleistocene are likely causes of the extinction of some Banksia species in Tasmania. Such extinctions may have been common in many taxonomic groups. The leaves and infructescences of Banksia kingii Jordan & Hill, sp. nov. are described from late Pleistocene sediments. This is the most recent macrofossil record of a now extinct species in Tasmania. Banksia kingii is related to the extant B. saxicola. Banksia strahanensis Jordan & Hill, sp. nov. (known only from a leaf and leaf fragments and related to B. spinulosa) is described from Early to Middle Pleistocene sediments in Tasmania. This represents the third Pleistocene macrofossil record of a plant species which is now extinct in Tasmania.


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