Vaccines

The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with Mycobacterium tuberculosis (M.tb) infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings. Full article

The ongoing coronavirus disease (COVID-19) pandemic is caused by a new coronavirus (severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)) first reported in Wuhan City, China. From there, it has been rapidly spreading to many cities inside and outside China. Nowadays, more than 110 million cases with deaths surpassing 2 million have been recorded worldwide, thus representing a major health and economic issues. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here, we demonstrated that the recombinantly expressed receptor-binding domain (RBD) of the spike protein can be coupled to immunologically optimized virus-like particles derived from cucumber mosaic virus (CuMV_TT). The RBD displayed CuMV_TT bound to ACE2, the viral receptor, demonstrating proper folding of RBD. Furthermore, a highly repetitive display of the RBD on CuMV_TT resulted in a vaccine candidate that induced high levels of specific antibodies in mice, which were able to block binding of the spike protein to ACE2 and potently neutralize SARS-CoV-2 virus in vitro. Full article

New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv. Full article

The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford–AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person, despite the European Medicines Agency (EMA) and the World Health Organization’s assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with the Oxford–AstraZeneca vaccine. This was a retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports, of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to pulmonary embolism; one fatality to thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA’s Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients’ characteristics and comorbidities, may enable assessment of the causality with higher specificity. Full article

Modified live vaccines (MLVs) against the porcine reproductive and respiratory syndrome virus (PRRSV) have been regularly associated with safety issues, such as reversion to virulence. In order to characterize the phenotypic and genetic evolution of the PRRSV-1 DV strain from the Porcilis^® PRRS MLV after limited passages in pigs, three in vivo experiments were performed. Trial#1 aimed (i) at studying transmission of the vaccine strain from vaccinated to unvaccinated contact pigs. Trial#2 and Trial#3 were designed (ii) to assess the reproducibility of Trial#1, using another vaccine batch, and (iii) to compare the virulence levels of two DV strains isolated from vaccinated (passage one) and diseased contact pigs (passage two) from Trial#1. DV strain isolates from vaccinated and contact pigs from Trial#1 and Trial#2 were submitted to Next-Generation Sequencing (NGS) full-genome sequencing. All contact animals from Trial#1 were infected and showed significantly increased viremia compared to vaccinated pigs, whereas no such change was observed during Trial#2. In Trial#3, viremia and transmission were higher for inoculated pigs with passage two of the DV strain, compared with passage one. In this study, we showed that the re-adaptation of the DV strain to pigs is associated with faster replication and increased transmission of the vaccine strain. Punctually, a decrease of attenuation of the DV vaccine strain associated with clinical signs and increased viremia may occur after limited passages in pigs. Furthermore, we identified three mutations linked to pig re-adaptation and five other mutations as potential virulence determinants. Full article

The COVID-19 pandemic is ongoing and we are still compiling new findings to decipher and understand SARS-CoV-2 infection during pregnancy. No reports encompass any conclusive confirmation of vertical transmission. Nevertheless, cases of fetal distress and multiple organ failure have been reported, as well as rare cases of fetal demise. While clinicians and scientists continue to seek proof of vertical transmission, they miss the greater point, namely the cause of preterm delivery. In this review, we suggest that the cause might not be due to the viral infection but the fetal exposure to maternal inflammation or cytokine storm that translates into a complication of COVID-19. This statement is extrapolated from previous experience with infections and inflammation which were reported to be fatal by increasing the risk of preterm delivery and causing abnormal neonatal brain development and resulting in neurological disorders like atypical behavioral phenotype or autistic syndrome. Given the potentially fatal consequences on neonate health, we highlight the urgent need for an animal model to study vertical transmission. The preclinical model will allow us to make the link between SARS-COV-2 infection, inflammation and long-term follow-up of child brain development. Full article

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail. Full article

COVID-19 is an ongoing pandemic caused by the highly infectious coronavirus SARS-CoV-2 that is engaging worldwide scientific research to find a timely and effective eradication strategy. Great efforts have been put into anti-COVID-19 vaccine generation in an effort to protect the world population and block SARS-CoV-2 spread. To validate the protective efficacy of the vaccination campaign and effectively control the pandemic, it is necessary to quantify the induction of neutralizing antibodies by vaccination, as they have been established to be a correlate of protection. In this work, a SARS-CoV-2 pseudovirus neutralization assay, based on a replication-incompetent lentivirus expressing an adapted form of CoV-2 S protein and an ACE2/TMPRSS2 stably expressing cell line, has been minimized in terms of protocol steps without loss of accuracy. The goal of the present simplified neutralization system is to improve SARS-CoV-2 vaccination campaign by means of an easy and accessible approach to be performed in any medical laboratory, maintaining the sensitivity and quantitative reliability of classical serum neutralization assays. Further, this assay can be easily adapted to different coronavirus variants by simply modifying the pseudotyping vector. Full article

Due to the aging population, modern society is facing an increasing prevalence of neurological diseases such as Alzheimer′s disease (AD). AD is an age-related chronic neurodegenerative disorder for which no satisfying therapy exists. Understanding the mechanisms underlying the onset of AD is necessary to find targets for protective treatment. There is growing awareness of the essential role of the immune system in the early AD pathology. Amyloidopathy, the main feature of early-stage AD, has a deregulating effect on the immune function. This is reciprocal as the immune system also affects amyloidopathy. It seems that the inflammatory reaction shows a heterogeneous pattern depending on the stage of the disease and the variation between individuals, making not only the target but also the timing of treatment important. The lack of relevant translational animal models that faithfully reproduce clinical and pathogenic features of AD is a major cause of the delay in developing new disease-modifying therapies and their optimal timing of administration. This review describes the communication between amyloidopathy and inflammation and the possibility of using nonhuman primates as a relevant animal model for preclinical AD research. Full article

Foot-and-mouth disease (FMD) is a highly contagious disease and one of the most economically important diseases of livestock. Vaccination is an important measure to control FMD and selection of appropriate vaccine strains is crucial. The objective of this study was to select a vaccine candidate and to evaluate the potential of a blocking ELISA for detecting neutralizing antibodies (NA-ELISA) in vaccine strain selection. Binary ethylenimine inactivated vaccines, prepared from four representative circulating strains (FMDV O/Mya/98, SCGH/CHA/2016, O/Tibet/99, and O/XJ/CHA/2017) belonging to four lineages within three different topotypes of FMD virus (FMDV) serotype O in China, were used to vaccinate cattle (12–13 animals for each strain), sheep (12–13 animals for each strain), and pigs (10 animals for each strain). The results of immunogenicity comparison showed that O/XJ/CHA/2017 exhibited the highest immunogenicity among the four strains in pigs, cattle, and sheep both by NA-ELISA and virus neutralizing test (VNT). Cross-neutralization analysis indicated that O/XJ/CHA/2017 displayed broad antigen spectrum and was antigenically matched with other three representative strains both by NA-ELISA and VNT. In addition, A significant correlation (p < 0.0001) was observed between the NA-ELISA titers and the VNT titers for four representative strains. The results showed that O/XJ/CHA/2017 was a promising vaccine strain candidate and NA-ELISA was comparable to VNT in neutralizing antibodies detection and could be used as the reference test system for vaccine strain selection. Full article

We developed an agent-based stochastic model, based on P Systems methodology, to decipher the effects of vaccination and contact tracing on the control of COVID-19 outbreak at population level under different control measures (social distancing, mask wearing and hand hygiene) and epidemiological scenarios. Our findings suggest that without the application of protection social measures, 56.1% of the Spanish population would contract the disease with a mortality of 0.4%. Assuming that 20% of the population was protected by vaccination by the end of the summer of 2021, it would be expected that 45% of the population would contract the disease and 0.3% of the population would die. However, both of these percentages are significantly lower when social measures were adopted, being the best results when social measures are in place and 40% of contacts traced. Our model shows that if 40% of the population can be vaccinated, even without social control measures, the percentage of people who die or recover from infection would fall from 0.41% and 56.1% to 0.16% and 33.5%, respectively compared with an unvaccinated population. When social control measures were applied in concert with vaccination the percentage of people who die or recover from infection diminishes until 0.10% and 14.5%, after vaccinating 40% of the population. Vaccination alone can be crucial in controlling this disease, but it is necessary to vaccinate a significant part of the population and to back this up with social control measures. Full article

The hard tick Ixodes ricinus is an obligate hematophagous arthropod and the main vector for several zoonotic diseases. The life cycle of this three-host tick species was completed for the first time in vitro by feeding all consecutive life stages using an artificial tick feeding system (ATFS) on heparinized bovine blood supplemented with glucose, adenosine triphosphate, and gentamicin. Relevant physiological parameters were compared to ticks fed on cattle (in vivo). All in vitro feedings lasted significantly longer and the mean engorgement weight of F₀ adults and F₁ larvae and nymphs was significantly lower compared to ticks fed in vivo. The proportions of engorged ticks were significantly lower for in vitro fed adults and nymphs as well, but higher for in vitro fed larvae. F₁-females fed on blood supplemented with vitamin B had a higher detachment proportion and engorgement weight compared to F₁-females fed on blood without vitamin B, suggesting that vitamin B supplementation is essential in the artificial feeding of I. ricinus ticks previously exposed to gentamicin. Full article

(1) Immunization with pneumococcal conjugate vaccines has decreased the burden of community-acquired pneumonia (CAP) in children and likely led to a shift in CAP etiology. (2) The Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) enrolled children 1-59 months with clinical CAP according to the World Health Organization (WHO) criteria at Sachs’ Children and Youth Hospital, Stockholm, Sweden. Children with rhonchi and indrawing underwent “bronchodilator challenge”. C-reactive protein and nasopharyngeal PCR detecting 20 respiratory pathogens, were collected from all children. Etiology was defined according to an a priori defined algorithm based on microbiological, biochemical, and radiological findings. (3) Of 327 enrolled children, 107 (32%) required hospitalization; 91 (28%) received antibiotic treatment; 77 (24%) had a chest X-ray performed; and 60 (18%) responded to bronchodilator challenge. 243 (74%) episodes were classified as viral, 11 (3%) as mixed viral-bacterial, five (2%) as bacterial, two (0.6%) as atypical bacterial and 66 (20%) as undetermined etiology. After exclusion of children responding to bronchodilator challenge, the proportion of bacterial and mixed viral-bacterial etiology was 1% and 4%, respectively. (4) The novel TREND etiology algorithm classified the majority of clinical CAP episodes as of viral etiology, whereas bacterial etiology was uncommon. Defining CAP in children <5 years is challenging, and the WHO definition of clinical CAP is not suitable for use in children immunized with pneumococcal conjugate vaccines. Full article

While the scientific community has been focusing on combating novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the current COVID-19 pandemic, we also want to draw your attention to this Special Issue of Vaccines entitled “Influenza Virus and Vaccine Development” [...] Full article

Vaccine hesitancy is a major threat to the success of COVID-19 vaccination programs. The present cross-sectional online survey of adult Poles (n = 1020) expressing a willingness to receive the COVID-19 vaccine was conducted between February and March 2021 and aimed to assess (i) the general trust in different types of vaccines, (ii) the level of acceptance of the COVID-19 vaccines already in use in Poland (BNT162b2 by BioNTech/Pfizer, mRNA-1273 by Moderna and AZD1222 by Oxford/AstraZeneca) as well as eight vaccines approved outside European Union (EU) or in advanced stages of clinical trials, (iii) level of fear of vaccination against COVID-19, and (iv) main sources of information on COVID-19 vaccination. Among all major vaccine technology, the highest level of trust was observed for the mRNA platform, with a considerable number of surveyed (>20%) not aware of the existence of vaccines produced using the traditional approach (inactivated and live attenuated vaccines). The age of participants was the main factor differentiating the level of trust in a particular vaccine type. Both BNT162b and mRNA-1273 received a high level of acceptance, contrary to AZD1222. From eight vaccines unauthorized in the EU at the moment of study, the CVnCoV (mRNA; CureVac) was met with the highest level of trust, followed by Ad26.COV2.S (vector; Janssen/Johnson&Johnson) and NVX-CoV2373 (protein; Novavax). Sputnik V (vector; Gamaleya Research Institute) was decidedly the least trusted vaccine. The median level of fear (measured by the 10-point Likert-type scale) in the studied group was 4.0, mostly related to the risk of serious allergic reactions, other severe adverse events and unknown long-term effects of vaccination. Female, individuals with a lower level of education and those not seeking any information on the COVID-19 vaccines revealed a higher fear of vaccination. Experts’ materials were the major source of information on COVID-19 vaccines in the studied group. The study shows the level of trust in COVID-19 vaccines can vary much across the producers while the mRNA vaccines are received with a high level of acceptance. It also emphasizes the need for effective and continuous science communication when fighting the pandemic as it may be an ideal time to increase the general awareness of vaccines. Full article

Herein, we compared the productivity of pigs inoculated with one of two classical swine fever (CSF) vaccines (low virulent of Miyagi (LOM) or Flc-LOM-BE^rns) plus the swine erysipelothrix rhusiopathiae (SE) vaccine. The feed intake and weight increase of the pigs inoculated with Flc-LOM-BE^rns + SE were normal. However, the feed intake of the pigs inoculated with LOM + SE dropped sharply from four days post-vaccination (dpv). In addition, the slaughter date was an average of eight days later than that of the pigs inoculated with Flc-LOM-BE^rns + SE. All pigs inoculated with the Flc-LOM-BE^rns + SE vaccine were completely differentiated at 14 days against CSF E^rns antibody and at approximately 45 days against the bovine viral diarrhea virus (BVDV) E^rns antibody; the titers were maintained until slaughter. Leucopenia occurred temporarily in the LOM + SE group, but not in the Flc-LOM-BE^rns + SE group. Expression of tumor necrosis factor (TNF)-α and IFN-γ was significantly (p < 0.05) higher in the LOM + SE group than in the mock (no vaccine) group. When conducting the same experiment on a breeding farm, the results were similar to those of the laboratory experiments. In conclusion, the biggest advantage of replacing the CSF LOM vaccine with the Flc-LOM-BE^rns vaccine is improved productivity. Full article

Background: The aims of the present study were to examine the prediction of the threat and coping appraisal utilizing an extended protection motivation theory (PMT) for the motivation to have COVID-19 vaccination and the influence of various information sources on coping appraisal among university students in China. Methods: The sample comprised 3145 students from 43 universities in China who completed an online survey including PMT constructs as well as constructs added to PMT. The PMT constructs comprised motivation to have COVID-19 vaccination, threat appraisal, and coping appraisal. The extended PMT constructs comprised knowledge about mechanisms and information sources of COVID-19 vaccination. Results: Perceived severity of COVID-19 was positively associated with motivation to have COVID-19 vaccination. Receiving information concerning COVID-19 vaccination from medical personnel was associated with greater self-efficacy, response efficacy, and knowledge, whereas receiving information concerning COVID-19 vaccination from coworkers/colleagues was associated with less response efficacy and knowledge. Receiving online information concerning COVID-19 vaccination was associated with greater response cost of vaccination efficacy and less knowledge. Conclusions: This study supported the prediction of perceived severity in the PMT for motivation to have COVID-19 vaccination among university students in China. Vaccination information sources have different effects on students’ coping appraisal of COVID-19 vaccination. Full article

The success of mass COVID-19 vaccination campaigns rests on widespread uptake. However, although vaccinations provide good protection, they do not offer full immunity and while they likely reduce transmission of the virus to others, the extent of this remains uncertain. This produces a dilemma for communicators who wish to be transparent about benefits and harms and encourage continued caution in vaccinated individuals but not undermine confidence in an important public health measure. In two large pre-registered experimental studies on quota-sampled UK public participants we investigate the effects of providing transparent communication—including uncertainty—about vaccination effectiveness on decision-making. In Study 1 (n = 2097) we report that detailed information about COVID-19 vaccines, including results of clinical trials, does not have a significant impact on beliefs about the efficacy of such vaccines, concerns over side effects, or intentions to receive a vaccine. Study 2 (n = 2217) addressed concerns that highlighting the need to maintain protective behaviours (e.g., social distancing) post-vaccination may lower perceptions of vaccine efficacy and willingness to receive a vaccine. We do not find evidence of this: transparent messages did not significantly reduce perceptions of vaccine efficacy, and in some cases increased perceptions of efficacy. We again report no main effect of messages on intentions to receive a vaccine. The results of both studies suggest that transparently informing people of the limitations of vaccinations does not reduce intentions to be vaccinated but neither does it increase intentions to engage in protective behaviours post-vaccination. Full article

In March 2021, the coronavirus disease 2019 (COVID-19) pandemic still poses a threat to the global population, and is a public health challenge that needs to be overcome. Now more than ever, action is needed to tackle vaccine hesitancy, especially in light of the availability of effective and safe vaccines. A cross-sectional online survey was carried out on a representative random sample of 1011 citizens from the Emilia-Romagna region, in Italy, in January 2021. The questionnaire collected information on socio-demographics, comorbidities, past vaccination refusal, COVID-19-related experiences, risk perception of infection, and likelihood to accept COVID-19 vaccination. Multiple logistic regression analyses and classification tree analyses were performed to identify significant predictors of vaccine hesitancy and to distinguish groups with different levels of hesitancy. Overall, 31.1% of the sample reported hesitancy. Past vaccination refusal was the key discriminating variable followed by perceived risk of infection. Other significant predictors of hesitancy were: ages between 35 and 54 years, female gender, low educational level, low income, and absence of comorbidities. The most common concerns about the COVID-19 vaccine involved safety (54%) and efficacy (27%). Studying the main determinants of vaccine hesitancy can help with targeting vaccination strategies, in order to gain widespread acceptance—a key path to ensure a rapid way out of the current pandemic emergency. Full article