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Understanding the dynamics of COVID-19; implications for therapeutic intervention, vaccine development and movement control

Salvamani S, Tan HZ, Thang WJ, Ter HC, Wan MS, Gunasekaran B, et al.

Br J Biomed Sci, 2020 Oct;77(4):168-184.
PMID: 32942955 DOI: 10.1080/09674845.2020.1826136

The COVID-19 disease is caused by the SARS-CoV-2 virus, which is highly infective within the human population. The virus is widely disseminated to almost every continent with over twenty-seven million infections and over ninety-thousand reported deaths attributed to COVID-19 disease. SARS-CoV-2 is a single stranded RNA virus, comprising three main viral proteins; membrane, spike and envelope. The clinical features of COVID-19 disease can be classified according to different degrees of severity, with some patients progressing to acute respiratory distress syndrome, which can be fatal. In addition, many infections are asymptomatic or only cause mild symptoms. As there is no specific treatment for COVID-19 there is considerable endeavour to raise a vaccine against SARS-CoV-2, in addition to engineering neutralizing antibody interventions. In the absence of an effective vaccine, movement controls of varying stringencies have been imposed. Whilst enforced lockdown measures have been effective, they may be less effective against the current strain of SARS-CoV-2, the G614 clade. Conversely, other mutations of the virus, such as the Δ382 variant could reduce the clinical relevance of infection. The front runners in the race to develop an effective vaccine focus on the SARS-Co-V-2 Spike protein. However, vaccines that produce a T-cell response to a wider range of SARS-Co-V-2 viral proteins, may be more effective. Population based studies that determine the level of innate immunity to SARS-CoV-2, from prior exposure to the virus or to other coronaviruses, will have important implications for government imposed movement control and the strategic delivery of vaccination programmes.

Matched MeSH terms: Viral Vaccines/therapeutic use
Nipah and Hendra virus infectious diseases

Yoneda M

Nippon Rinsho, 2016 12;74(12):1973-1978.
PMID: 30550652

Nipah and Hendra virus were first identified in mid 1990s in Australia and Malaysia, caus- ing epidemics with high mortality rate in affected animals and humans. Since their first emer- gence, they continued to re-emerge in Australia and South East Asia almost every year. Nipah and Hendra virus were classified in the new genus Henipavirus because of their un- common features amongst Paramyxoviridae. Henipaviruses are zoonotic paramyxoviruses with a broad tropism, and cause severe acute respiratory disease and encephalitis. Their high virulence and wide host range make them to be given Biosecurity Level 4 status. This review summarizes details of Henipavirus emergence, reservoir hosts and pathology, and introduce recent progress in vaccines and antivirals.

Matched MeSH terms: Viral Vaccines/therapeutic use
Fulltext Status of vaccine research and development of vaccines for Nipah virus

Satterfield BA, Dawes BE, Milligan GN

Vaccine, 2016 06 03;34(26):2971-2975.
PMID: 26973068 DOI: 10.1016/j.vaccine.2015.12.075

Nipah virus (NiV) is a highly pathogenic, recently emerged paramyxovirus that has been responsible for sporadic outbreaks of respiratory and encephalitic disease in Southeast Asia. High case fatality rates have also been associated with recent outbreaks in Malaysia and Bangladesh. Although over two billion people currently live in regions in which NiV is endemic or in which the Pteropus fruit bat reservoir is commonly found, there is no approved vaccine to protect against NiV disease. This report examines the feasibility and current efforts to develop a NiV vaccine including potential hurdles for technical and regulatory assessment of candidate vaccines and the likelihood for financing.

Matched MeSH terms: Viral Vaccines/therapeutic use*
Fulltext Status of research and development of vaccines for enterovirus 71

Reed Z, Cardosa MJ

Vaccine, 2016 06 03;34(26):2967-2970.
PMID: 26973065 DOI: 10.1016/j.vaccine.2016.02.077

Although outbreaks of Hand, Foot, and Mouth Disease (HFMD) in young children have long been recognized worldwide, the occurrence of rare and life-threatening neurological, respiratory, and cardiac complications has propelled this common condition into the spotlight as a major public health problem in the affected countries. Various enteroviruses cause HFMD, but the severe complications have been mostly associated with enterovirus 71 (EV71). Medical treatment is supportive and measures to interrupt transmission have been challenging to implement. Preventive vaccines could have an important clinical impact, especially among children younger than 3 years old who are most susceptible to the neurological complications. Several groups in the highly affected Asia-Pacific region are working towards vaccines against EV71 and some candidates have progressed to late-stage clinical trials with two vaccines recently reported to have been approved by the regulatory authorities in China. This report summarizes current issues and progress in the development of vaccines against EV71.

Matched MeSH terms: Viral Vaccines/therapeutic use*
Fulltext Hendra virus and Nipah virus animal vaccines

Broder CC, Weir DL, Reid PA

Vaccine, 2016 06 24;34(30):3525-34.
PMID: 27154393 DOI: 10.1016/j.vaccine.2016.03.075

Hendra virus (HeV) and Nipah virus (NiV) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. HeV appeared in Queensland, Australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. NiV emerged a few years later in Malaysia and Singapore in 1998-1999 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. The key pathological elements of HeV and NiV infection in several species of mammals, and also in people, are a severe systemic and often fatal neurologic and/or respiratory disease. In people, both HeV and NiV are also capable of causing relapsed encephalitis following recovery from an acute infection. The known reservoir hosts of HeV and NiV are several species of pteropid fruit bats. Spillovers of HeV into horses continue to occur in Australia and NiV has caused outbreaks in people in Bangladesh and India nearly annually since 2001, making HeV and NiV important transboundary biological threats. NiV in particular possesses several features that underscore its potential as a pandemic threat, including its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals, along with a capacity of limited human-to-human transmission. Several HeV and NiV animal challenge models have been developed which have facilitated an understanding of pathogenesis and allowed for the successful development of both active and passive immunization countermeasures.

Matched MeSH terms: Viral Vaccines/therapeutic use*
An investigation of the seroprevalence of CrimeanCongo Hemorrhagic Fever and Lumpy Skin Disease in domesticated water buffaloes in northern Turkey

Okur-Gumusova S, Tamer C, Ozan E, Cavunt A, Kadi H, Muftuoglu B, et al.

Trop Biomed, 2020 Mar 01;37(1):165-173.
PMID: 33612727

This study was conducted in Samsun Province of Turkey to investigate the serological status of domesticated water buffaloes for both Crimean-Congo Hemorrhagic Fever (CCHF) and Lumpy Skin Disease (LSD). Serum was collected from a total of 272 water buffaloes from different age groups and both genders; of the total, 48.1% had been vaccinated against LSD with heterologous sheep-goat pox vaccine. The serum samples were individually assessed by using a commercial ID screen enzyme-linked immune-sorbent assay (ELISA) to detect neutralizing antibodies against both CCHF virus and LSD virus. All 272 buffaloes were negative for antibodies against the CCHF virus. All the unvaccinated buffaloes (141) were seronegative for LSD virus but of the 131 vaccinated buffaloes, 10 (7.6%) were seropositive for the LSD virus. In addition, 8.6% of vaccinated animals age >1 year old were seropositive for LSD, whereas the seropositivity was 5.1% for the animals age <= 1 year old. There was no significant difference for seropositivity between male and female animals in the >1 year old or <= 1 year old age groups. When seroprevalances for LSD in the tested water buffaloes are evaluated by gender, there was a significant difference between females (8.6%) and males (0%) in the <1 year old water buffaloes (X2=20.24; P<0.001). Separately, the results of this study indicate that Bafra district water buffaloes are not infected by CCHFV and LSDV and some of the buffaloes that vaccinated with LSDV did not develop sufficient antibodies to protect them after they were vaccinated for the LSD virus. Furthermore, the authors of this study conclude that both the commercially produced vaccine that is currently administered and the vaccination strategy have to be urgently evaluated by the veterinary authorities in Turkey. This is essential in order to combat the spread of LSD virus infection with an effective vaccine and a comprehensive management strategy across Turkey.

Matched MeSH terms: Viral Vaccines/therapeutic use
Flavivirus infection-A review of immunopathogenesis, immunological response, and immunodiagnosis

Chong HY, Leow CY, Abdul Majeed AB, Leow CH

Virus Res, 2019 12;274:197770.
PMID: 31626874 DOI: 10.1016/j.virusres.2019.197770

Flaviviruses are group of single stranded RNA viruses that cause severe endemic infection and epidemics on a global scale. It presents a significant health impact worldwide and the viruses have the potential to emerge and outbreak in a non-endemic geographical region. Effective vaccines for prophylaxis are only available for several flaviviruses such as Yellow Fever virus, Tick-borne Encephalitis Virus, Dengue Virus and Japanese Encephalitis Virus and there is no antiflaviviral agent being marketed. This review discusses the flavivirus genome, replication cycle, epidemiology, clinical presentation and pathogenesis upon infection. Effective humoral response is critical to confer protective immunity against flaviviruses. Hence, we have also highlighted the immune responses elicited upon infection, various diagnostic facilities available for flaviviral disease and monoclonal antibodies available to date against flavivirus infection.

Matched MeSH terms: Viral Vaccines/therapeutic use
COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development

Aljabali AAA, Bakshi HA, Satija S, Metha M, Prasher P, Ennab RM, et al.

Pharm Nanotechnol, 2020;8(4):323-353.
PMID: 32811406 DOI: 10.2174/2211738508999200817163335

BACKGROUND: The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.
OBJECTIVES: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.
METHODS: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.
RESULTS: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures.
Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.

Matched MeSH terms: Viral Vaccines/therapeutic use*
Development of Novel miRNA-based Vaccines and Antivirals against Enterovirus 71

Yee PT, Poh CL

Curr Pharm Des, 2016;22(44):6694-6700.
PMID: 27510488 DOI: 10.2174/1381612822666160720165613

The Hand, Foot and Mouth Disease (HFMD) is caused by Enterovirus 71 (EV-A71) and Coxsackieviruses. Common HFMD symptoms are high fever (≥ 39°C), rashes, and ulcers but complications due to virulent EV-A71 may arise leading to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents. Recent studies have reported the emergence of novel antiviral agents and vaccines that utilize microRNAs (miRNAs). They belong to a class of small (19-24 nt) non coding RNA molecules. As miRNAs play a major role in the host regulatory system, there is a huge opportunity for interplay between host miRNAs and EV-A71 expressions. A total of 42 out of 64 miRNAs were up-regulated in EV-A71-infected cells. There was consistent up-regulation of miR-1246 gene expression that targeted the DLG3 gene which contributes to neurological pathogenesis. In contrast, miR-30a that targets calcium channels for membrane transportation was down-regulated. This leads to repression of EV-A71 replication. The impact of host miRNAs on immune activation, shutdown of host protein synthesis, apoptosis, signal transduction and viral replication are discussed. miRNAs have been used in the construction of live attenuated vaccines (LAV) such as the poliovirus LAV that has miRNA binding sites for let-7a or miR-124a. The miRNAbearing vaccine will not replicate in neuronal cells carrying the corresponding miRNA but could still replicate in the gastrointestinal tract and hence remains to act as immunogens. As such, miRNAs are attractive candidates to be developed as vaccines and antivirals.

Matched MeSH terms: Viral Vaccines/therapeutic use
Fulltext Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective

Chan Y, Ng SW, Singh SK, Gulati M, Gupta G, Chaudhary SK, et al.

Life Sci, 2021 Sep 01;280:119744.
PMID: 34174324 DOI: 10.1016/j.lfs.2021.119744

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.

Matched MeSH terms: Viral Vaccines/therapeutic use
Serological response of cattle to simultaneous vaccinations against foot-and-mouth disease and haemorrhagic septicaemia

Joseph PG, Hedger RS

Vet Rec, 1984 May 19;114(20):494-6.
PMID: 6330961

In Malaysia, where vaccination campaigns against foot-and-mouth disease and haemorrhagic septicaemia are routinely carried out, it was desirable to determine whether it was safe and efficacious to administer both vaccines simultaneously. A trial group of 104 cattle was divided into three groups; group 1 animals received both vaccines simultaneously, group 2 animals received only foot-and-mouth disease vaccine and group 3 animals received only haemorrhagic septicaemia vaccine. The serological response to vaccinations was monitored at 0, 21 and 35 days by the virus neutralisation test for foot-and-mouth disease and the mouse-protection and indirect haemagglutination tests for haemorrhagic septicaemia. The simultaneous administration of the two inactivated vaccines produced no adverse effects and the serological response did not differ from the response to either vaccine given separately, thus indicating that cattle may be safely and effectively vaccinated simultaneously in this way.

Matched MeSH terms: Viral Vaccines/therapeutic use
Recombinant nipah virus vaccines protect pigs against challenge

Weingartl HM, Berhane Y, Caswell JL, Loosmore S, Audonnet JC, Roth JA, et al.

J Virol, 2006 Aug;80(16):7929-38.
PMID: 16873250

Nipah virus (NiV), of the family Paramyxoviridae, was isolated in 1999 in Malaysia from a human fatality in an outbreak of severe human encephalitis, when human infections were linked to transmission of the virus from pigs. Consequently, a swine vaccine able to abolish virus shedding is of veterinary and human health interest. Canarypox virus-based vaccine vectors carrying the gene for NiV glycoprotein (ALVAC-G) or the fusion protein (ALVAC-F) were used to intramuscularly immunize four pigs per group, either with 10(8) PFU each or in combination. Pigs were boosted 14 days postvaccination and challenged with 2.5 x 10(5) PFU of NiV two weeks later. The combined ALVAC-F/G vaccine induced the highest levels of neutralization antibodies (2,560); despite the low neutralizing antibody levels in the F vaccinees (160), all vaccinated animals appeared to be protected against challenge. Virus was not isolated from the tissues of any of the vaccinated pigs postchallenge, and a real-time reverse transcription (RT)-PCR assay detected only small amounts of viral RNA in several samples. In challenge control pigs, virus was isolated from a number of tissues (10(4.4) PFU/g) or detected by real-time RT-PCR. Vaccination of the ALVAC-F/G vaccinees appeared to stimulate both type 1 and type 2 cytokine responses. Histopathological findings indicated that there was no enhancement of lesions in the vaccinees. No virus shedding was detected in vaccinated animals, in contrast to challenge control pigs, from which virus was isolated from the throat and nose (10(2.9) PFU/ml). Based on the data presented, the combined ALVAC-F/G vaccine appears to be a very promising vaccine candidate for swine.

Matched MeSH terms: Viral Vaccines/therapeutic use*
Fulltext All together to Fight COVID-19

Momtazmanesh S, Ochs HD, Uddin LQ, Perc M, Routes JM, Vieira DN, et al.

Am J Trop Med Hyg, 2020 06;102(6):1181-1183.
PMID: 32323644 DOI: 10.4269/ajtmh.20-0281

Novel coronavirus disease (COVID-19), named a pandemic by the WHO, is the current global health crisis. National and international collaboration are indispensable for combating COVID-19 and other similar potential outbreaks. International efforts to tackle this complex problem have led to remarkable scientific advances. Yet, as a global society, we can and must take additional measures to fight this pandemic. Undoubtedly, our approach toward COVID-19 was not perfect, and testing has not been deployed fast enough to arrest the epidemic early on. It is critical that we revise our approaches to be more prepared for pandemics as a united body by promoting global cooperation and commitment.

Matched MeSH terms: Viral Vaccines/therapeutic use

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