Nipah virus (NiV), a bat-borne paramyxovirus, results in neurological and respiratory diseases with high mortality in humans and animals. Developing vaccines is crucial for fighting these diseases. Previously, only a few studies focused on the fusion (F) protein alone as the immunogen. Numerous NiV strains have been identified, including 2 representative strains from Malaysia (NiV-M) and Bangladesh (NiV-B), which differ significantly from each other. In this study, an F protein sequence with the potential to prevent different NiV strain infections was designed by bioinformatics analysis after an in-depth study of NiV sequences in GenBank. Then, a chimpanzee adenoviral vector vaccine and a DNA vaccine were developed. High levels of immune responses were detected after AdC68-F, pVAX1-F, and a prime-boost strategy (pVAX1-F/AdC68-F) in mice. After high titers of humoral responses were induced, the hamsters were challenged by the lethal NiV-M and NiV-B strains separately. The vaccinated hamsters did not show any clinical signs and survived 21 days after infection with either strain of NiV, and no virus was detected in different tissues. These results indicate that the vaccines provided complete protection against representative strains of NiV infection and have the potential to be developed as a broad-spectrum vaccine for human use.

The recent centennial anniversary of R.E. Montgomery\'s seminal published description of \"a form of swine fever\" disease transmitted from wild African pigs to European domestic pigs is a call to action to accelerate African Swine Fever (ASF) vaccine research and development. ASF modified live virus (MLV) first-generation gene deleted vaccine candidates currently offer the most promise to meet international and national guidelines and regulatory requirements for veterinary product licensure and market authorization. A major, rate-limiting impediment to the acceleration of current as well as future vaccine candidates into regulatory development is the absence of internationally harmonized standards for assessing vaccine purity, potency, safety, and efficacy. This review summarizes the asymmetrical landscape of peer-reviewed published literature on ASF MLV vaccine approaches and lead candidates, primarily studied to date in the research laboratory in proof-of-concept or early feasibility clinical safety and efficacy studies. Initial recommendations are offered toward eventual consensus of international harmonized guidelines and standards for ASF MLV vaccine purity, potency, safety, and efficacy. To help ensure the successful regulatory development and approval of ASF MLV first generation vaccines by national regulatory associated government agencies, the World Organisation for Animal Health (WOAH) establishment and publication of harmonized international guidelines is paramount.

Despite the passage of over 30 years since its discovery, the importance of feline immunodeficiency virus (FIV) on the health and longevity of infected domestic cats is hotly debated amongst feline experts. Notwithstanding the absence of good quality information, Australian and New Zealand (NZ) veterinarians should aim to minimise the exposure of cats to FIV. The most reliable way to achieve this goal is to recommend that all pet cats are kept exclusively indoors, or with secure outdoor access (e.g., cat enclosures, secure gardens), with FIV testing of any in-contact cats. All animal holding facilities should aim to individually house adult cats to limit the spread of FIV infection in groups of animals that are stressed and do not have established social hierarchies. Point-of-care (PoC) FIV antibody tests are available in Australia and NZ that can distinguish FIV-infected and uninfected FIV-vaccinated cats (Witness™ and Anigen Rapid™). Although testing of whole blood, serum or plasma remains the gold standard for FIV diagnosis, PoC testing using saliva may offer a welfare-friendly alternative in the future. PCR testing to detect FIV infection is not recommended as a screening procedure since a negative PCR result does not rule out FIV infection and is only recommended in specific scenarios. Australia and NZ are two of three countries where a dual subtype FIV vaccine (Fel-O-Vax® FIV) is available and offers a further avenue for disease prevention. Since FIV vaccination only has a reported field effectiveness of 56% in Australia, and possibly lower in NZ, FIV-vaccinated cats should undergo annual FIV testing prior to annual FIV re-vaccination using a suitable PoC kit to check infection has not occurred in the preceding year. With FIV-infected cats, clinicians should strive to be even more thorough than usual at detecting early signs of disease. The most effective way to enhance the quality of life and life expectancy of FIV-infected cats is to optimise basic husbandry and to treat any concurrent conditions early in the disease course. Currently, no available drugs are registered for the treatment of FIV infection. Critically, the euthanasia of healthy FIV-infected cats, and sick FIV-infected cats without appropriate clinical investigations, should not occur.

Vaccination is currently the most effective strategy to control porcine reproductive and respiratory syndrome (PRRS). New-generation PRRS vaccines are required to be safe and broadly cross-protective. We have recently created the chimeric PRRS virus K418DM which proved to be a good vaccine candidate under field conditions. In the present study, we designed safety and efficacy tests under experimental and field conditions for further evaluation of K418DM1.1, a plaque-purified K418DM. In the homologous challenge study, K418DM1.1 induced high serum virus neutralization (SVN) antibody titers (i.e., 4.2 log2 ± 1.7) at 21 days post-challenge (dpc) and provided protection as demonstrated by the significantly lower levels of viremia at 3 and 7 dpc and significantly lower microscopic lung lesion scores compared to the unvaccinated group. K418DM1.1 was also protective in the heterologous challenge study, with vaccinated pigs showing significantly lower levels of viremia at 14 dpc compared to the unvaccinated pigs. A field study was performed to evaluate the efficacy of K418DM1.1 against heterologous exposure and vaccinated pigs presented significantly lower viremia than unvaccinated pigs. According to the safety test for the examination of virulence reversion, no infectivity was observed in tissue homogenate filtrate both in the vaccinated and comingled groups. Thus, the risk of virulence, as well as transmission, appeared negligible. These overall results indicate that K418DM1.1 is a good vaccine candidate based on its safety and protective efficacy.

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This paper makes the case for immediate planning for a COVID-19 vaccination uptake strategy in advance of vaccine availability for two reasons: first, the need to build a consensus about the order in which groups of the population will get access to the vaccine; second, to reduce any fear and concerns that exist in relation to vaccination and to create demand for vaccines. A key part of this strategy is to counter the anti-vaccination movement that is already promoting hesitancy and resistance. Since the beginning of the COVID-19 pandemic there has been a tsunami of misinformation and conspiracy theories that have the potential to reduce vaccine uptake. To make matters worse, sections of populations in many countries display low trust in governments and official information about the pandemic and how the officials are tackling it. This paper aims to set out in short form critical guidelines that governments and regional bodies should take to enhance the impact of a COVID-19 vaccination strategy. We base our recommendations on a review of existing best practice guidance. This paper aims to assist those responsible for promoting COVID-19 vaccine uptake to digest the mass of guidance that exists and formulate an effective locally relevant strategy. A summary of key guidelines is presented based on best practice guidance.

There is a pressing need for new vaccines against alphaviruses, which can cause fatal encephalitis (Venezuelan equine encephalitis virus (VEEV) and others) and severe arthralgia (e.g. Chikungunya virus, CHIKV). These positive-strand RNA viruses are diverse and evolve rapidly, meaning that the sequence of any vaccine should cover multiple strains that may be quite different from any previous isolate. Here, consensus proteins were produced to represent the common physicochemical properties (PCPs) of the epitope rich, B domain of the E2 envelope protein. PCP-consensus proteins were based on multiple strains of VEEV (VEEVcon) and CHIKV (CHIKVcon) or the conserved PCPs of 24 different alphaviruses (AllAVcon). The AllAVcon was altered to include binding sites for neutralizing antibodies of both VEEV and CHIKV strains (Mosaikcon). All four designed proteins were produced solubly in E. coli and purified. They formed the β-strand core expected from experimental structures of this region of the wild type E2 proteins as indicated by circular dichroism (CD) spectra. Furthermore, the CHIKVcon protein bound to a structure dependent, CHIKV neutralizing monoclonal antibody. The AllAVcon and Mosaikcon proteins bound to polyclonal antibodies generated during natural infection with either VEEV or CHIKV, indicating they contained epitopes of both serotypes. The Mosaikcon antigen induced antibodies in rabbit sera that recognized both the VEEVcon and CHIKVcon spike proteins. These PCP-consensus antigens are promising starting points for novel, broad-spectrum alphavirus vaccines.

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of \"disease enhancement\" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.

Global fatalities related to COVID-19 are expected to be high in 2020-2021. Developing and delivering a vaccine may be the most likely way to end the pandemic. If it were possible to shorten this development time by weeks or months, this may have a significant effect on reducing deaths. Phase II and phase III trials could take less long to conduct if they used human challenge methods-that is, deliberately infecting participants with COVID-19 following inoculation. This article analyses arguments for and against such methods and provides suggested broad guidelines for regulators, researchers and ethics committees when considering these matters. It concludes that it may be possible to maintain current ethical standards yet still permit human challenge trials in a context where delay is critical. The implications are that regulators and researchers need to work together now to design robust but short trials and streamline ethics approval processes so that they are in place when applications for trials are made.

BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies.
OBJECTIVE: To review, from an Infectious Diseases perspective, the safety profile of agents targeting tumour necrosis factor-α (TNF-α) and to suggest preventive recommendations.
METHODS: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family.
BACKGROUND: Preclinical and clinical evidence indicate that anti-TNF-α therapy (infliximab, adalimumab, golimumab, certolizumab pegol and etanercept) is associated with a two-to four-fold increase in the risk of active tuberculosis and other granulomatous conditions (mostly resulting from the reactivation of a latent infection). In addition, it may lead to the occurrence of other serious infections (bacterial, fungal, opportunistic and certain viral infections). These associated risks seem to be lower for etanercept than other agents. Screening for latent tuberculosis infection should be performed before starting anti-TNF-α therapy, followed by anti-tuberculosis therapy if appropriate. Screening for chronic hepatitis B virus (HBV) infection is also recommended, and antiviral prophylaxis may be warranted for hepatitis B surface antigen-positive individuals. No benefit is expected from the use of antibacterial, anti-Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate antiviral vaccinations (i.e. influenza) should be administered. Live-virus vaccines (i.e. varicella-zoster virus or measles-mumps-rubella) may be contraindicated in people receiving anti-TNF-α therapy, although additional data are needed before definitive recommendations can be made.
CONCLUSIONS: Prevention measures should be implemented to reduce the risk of latent tuberculosis or HBV reactivation among individuals receiving anti-TNF-α therapy.