Vaccines

Salmonellosis remains a major medical and an unmet socioeconomic challenge. Worldwide, more than three million deaths per year are associated with Salmonella enterica serovar Enteritidis infections. Although commercially available vaccines for use in poultry exist, their efficacy is limited. We previously described a method for isolating a heat extract (HE) fraction of the cell surface of S. Enteritidis that contained major antigenic complexes immunogenic in hens naturally infected with the bacterium. One single dose of S. Enteritidis’ HE induced protection against lethal salmonellosis in mice. Furthermore, HE encapsulation in nanoparticles of the copolymer of methyl vinyl ether and maleic anhydride (PVM/MA), Gantrez AN, improved and prolonged the protection against the disease in mice. We formulated new preparations of Gantrez AN nanoparticles with HE S. Enteritidis and assessed their stability in drinking water and their efficacy in hens after experimental infection. The oral treatment of six-week-old hens with two doses of HE nanoparticles significantly reduced the Salmonella excretion in hens. Due to the effectiveness of the treatment in reducing bacterial excretion, we conclude that HE nanoencapsulation obtained from S. Enteritidis is a viable novel vaccination approach against salmonellosis in farms. Full article

Feeble cellular responses induced by T cell-based vaccines are a major challenge for the development of an effective vaccine against Hepatitis C virus (HCV) infection. To address this challenge, the potential of N-terminal fragment of gp96 heat shock protein (rNT (gp96) as an adjuvant was evaluated and compared to that of the CpG (as a recognized Th1-type adjuvant) in the formulation of HCV core/NS3 antigens in three immunization strategies of protein/protein, DNA/DNA, and DNA/protein. Immunized mice were evaluated for elicited immune responses in week 3 (W3) and 11 post-immunizations. Our results demonstrated that the protein (subunit) vaccine formulated with rNT (gp96) in protein/protein strategy (core/NS3 + gp96) was significantly more efficient than CpG oligodeoxynucleotides (CpG ODN) formulation and all other immunization strategies in the induction of Th1-type cytokines. This group of mice (core/NS3 + gp96) also elicited a high level of anti-Core-NS3 total immunoglobulin G (IgG) with dominant IgG2a isotype at W3. Thus, the co-administration of recombinant NT (gp96) protein with rHCV proteins might be a promising approach in the formulation of HCV subunit vaccine candidates for induction of high levels of Th1 cytokines and humoral responses. Full article

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world’s population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects. Full article

Biologics can be combined with liquid polymer materials and electrospun to produce a dry nanofibrous scaffold. Unlike spray-drying and freeze-drying, electrospinning minimizes the physiological stress on sensitive materials, and nanofiber mat properties such as hydrophobicity, solubility, and melting temperature can be tuned based on the polymer composition. In this study, we explored the dry formulation of a virus-like particle (VLP) vaccine by electrospinning VLP derived from rabbit hemorrhagic disease virus modified to carry the MHC-I gp100 tumor-associated antigen epitope. VLP were added to a polyvinylpyrrolidone (PVP) solution (15% w/v) followed by electrospinning at 24 kV. Formation of a nanofibrous mat was confirmed by scanning electron microscopy, and the presence of VLP was confirmed by transmission electron microscopy and Western blot. VLP from the nanofibers induced T-cell activation and interferon- (IFN-) γ production in vitro. To confirm in vivo cytotoxicity, Pmel mice treated by injection with gp100 VLP from nanofibers induced a gp100 specific immune response, lysing approximately 65% of gp100-pulsed target cells, comparable to mice vaccinated with gp100 VLP in PBS. VLP from nanofibers also induced an antibody response. This work shows that electrospinning can be used to dry-formulate VLP, preserving both humoral and cell-mediated immunity. Full article

Background: Elderly population is considered at high risk for pneumococcal diseases. The pneumococcal vaccine coverage presents extremely low among elderly people in China. However, the serious event of COVID-19 drives interest in the pneumococcal vaccine, prompting us investigating the willingness to accept the 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influencing factors among people aged over 60 years during the COVID-19 pandemic. Methods: A cross-sectional study was employed using a self-administered questionnaire in Shenzhen City of China, elaborating the willingness toward PPSV23 in the elderly persons. Binomial logistic analyses were performed to estimate the influencing factors using odds ratios (ORs) and 95% confidence interval (CI). Results: Among 15,066 respondents, 91.5% presented a positive attitude toward PPSV23. Logistic analyses suggested the influencing factors included knowledge about pneumonia (adjusted OR [aOR] 1.391, 95%CI 1.214–1.593), perception of the seriousness of pneumonia (aOR 1.437, 95%CI 1.230–1.680) and preventing way for pneumonia (aOR 1.639, 95%CI 1.440–1.865), worried about getting pneumonia (aOR 2.751, 95%CI 2.444–3.096), understanding vaccine policy (aOR 1.774, 95%CI 1.514–2.079), and influenza vaccine (aOR 3.516 and 95%CI 2.261–5.468) and PPSV23 histories (aOR 3.199, 95%CI 1.492–6.860). Conclusions: The interest surge in pneumococcal vaccine coincided with the COVID-19 outbreak, foreshadowing higher demand for pneumococcal vaccine in the near future. Full article

According to an analysis of published data, only 20% of patients with the new coronavirus infection develop severe life-threatening complications. Currently, there are no known biomarkers, the determination of which before the onset of the disease would allow assessing the likelihood of its severe course. The purpose of this literature review was to analyze possible genetic factors characterizing the immune response to the new coronavirus infection that could be associated with the expression of angiotension-converting enzyme 2 (ACE-2) and related proteins as predictors of severe Corona virus disease 2019 (COVID-19). We analyzed original articles published in Medline, PubMed and Scopus databases from December 2019 to November 2020. For searching articles, we used the following keywords: New coronavirus infection, Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), COVID-19, severe course, complications, thrombosis, cytokine storm, ACE-2, biomarkers. In total, 3714 publications were selected using the keywords, of which 8 were in congruence with all the criteria. The literature analysis of the association of immunogenic characteristics and the expression of ACE-2 and related proteins with the development of severe COVID-19 revealed following genetic factors: HLA-B*46:01 genotype, CXCR6 gene hypoexpression, CCR9 gene expression, TLR7, rs150892504 mutations in the ERAP2 gene, overexpression of wild-type ACE-2, TMPRSS2 and its different polymorphisms. Genes, associated with the severe course, are more common among men. According to the analysis data, it can be assumed that there are population differences. However, the diagnostic significance of the markers described must be confirmed with additional clinical studies. Full article

Vaccination could be a key protective measure against coronavirus disease 2019 (COVID-19), and it is important to understand the acceptability of the COVID-19 vaccine among the general public. However, there is no study on the acceptance of a COVID-19 vaccine in Japan. Therefore, this study aimed to describe the COVID-19 vaccine acceptance and hesitancy situation in Japan and assess the factors associated with such issues. This was a cross-sectional study based on an internet survey completed by 2956 people. Participants were asked to indicate how likely they were to get vaccinated for COVID-19. In addition, the participants responded to questions regarding sociodemographic factors, attitudes, and beliefs regarding COVID-19 infection and vaccination. The proportion of participants with a high likelihood of getting a COVID-19 vaccine was 62.1%. Multiple logistic regression analysis showed that vaccine acceptance was lower among several sociodemographic groups, such as women, adults aged 20–49 years, and those with a low-income level. Several psychological factors, especially the perceived effectiveness of the COVID-19 vaccine, and willingness to protect others by getting oneself vaccinated, were associated with vaccine acceptance. Our results indicate that the perceived effectiveness of the vaccine and willingness to protect others may play an important role in the acceptance of the COVID-19 vaccine. Full article

Streptococcus pneumoniae (Spn) is a bacterial pathogen known to colonize the upper respiratory tract and cause serious opportunistic diseases such as pneumonia, bacteremia, sepsis and meningitis. As a consequence, millions of attributable deaths occur annually, especially among infants, the elderly and immunocompromised individuals. Although current vaccines, composed of purified pneumococcal polysaccharide in free form or conjugated to a protein carrier, are widely used and have been demonstrated to be effective in target groups, Spn has continued to colonize and cause life-threatening disease in susceptible populations. This lack of broad protection highlights the necessity of improving upon the current “gold standard” pneumococcal vaccines to increase protection both by decreasing colonization and reducing the incidence of sterile-site infections. Over the past century, most of the pneumococcal proteins that play an essential role in colonization and pathogenesis have been identified and characterized. Some of these proteins have the potential to serve as antigens in a multi-valent protein vaccine that confers capsule independent protection. This review seeks to summarize the benefits and limitations of the currently employed vaccine strategies, describes how leading candidate proteins contribute to pneumococcal disease development, and discusses the potential of these proteins as protective antigens – including as a hybrid construct. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe respiratory distress and reproductive failure in swine. Modified live virus (MLV) vaccines provide the highest degree of protection and are most often the preferred choice. While somewhat protective, the use of MLVs is accompanied by multiple safety issues, why safer alternatives are urgently needed. Here, we describe the generation of virus replicon particles (VRPs) based on a classical swine fever virus genome incapable of producing infectious progeny and designed to express conserved PRRSV-2 cytotoxic T-cell epitopes. Eighteen pigs matched with the epitopes by their swine leucocyte antigen-profiles were vaccinated (N = 11, test group) or sham-vaccinated (N = 7, control group) with the VRPs and subsequently challenged with PRRSV-2. The responses to vaccination and challenge were monitored using serological, immunological, and virological analyses. Challenge virus load in serum did not differ significantly between the groups, whereas the virus load in the caudal part of the lung was significantly lower in the test group compared to the control group. The number of peptide-induced interferon-γ secreting cells after challenge was higher and more frequent in the test group than in the control group. Together, our results provide indications of a shapeable PRRSV-specific cell-mediated immune response that may inspire future development of effective PRRSV vaccines. Full article

Between June and November 2020, we assessed plasma antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein in 4996 participants (aged 18–82 years, 34.5% men) from the National and Kapodistrian University of Athens. The weighted overall prevalence was 1.6% and monthly prevalence correlated with viral RNA-confirmed SARS-CoV-2 infections in Greece, in the same period. Notably, 49% of seropositive cases reported no history of SARS-CoV-2 infection-related clinical symptoms and 33% were unsuspected of their previous infection. Additionally, levels of anti-SARS-CoV-2 antibodies against the spike-protein receptor-binding domain were similar between symptomatic and asymptomatic individuals, irrespective of age and gender. Using Food and Drug Administration Emergency Use Authorization-approved assays, these results support the need for such studies on pandemic evaluation and highlight the development of robust humoral immune responses even among asymptomatic individuals. The high percentage of unsuspected/asymptomatic active cases, which may contribute to community transmission for more days than that of cases who are aware and self-isolate, underscores the necessity of measures across the population for the efficient control of the pandemic. Full article

It is important to detect signals of abrupt changes in adverse event reporting in order to notice public safety concerns and take prompt action, especially for vaccines under national immunization programs. In this study, we assessed the applicability of change point analysis (CPA) for signal detection in vaccine safety surveillance. The performances of three CPA methods, namely Bayesian change point analysis, Taylor’s change point analysis (Taylor-CPA), and environmental time series change point detection (EnvCpt), were assessed via simulated data with assumptions for the baseline number of events and degrees of change. The analysis was validated using the Korea Adverse Event Reporting System (KAERS) database. In the simulation study, the Taylor-CPA method exhibited better results for the detection of a change point (accuracy of 96% to 100%, sensitivity of 7% to 100%, specificity of 98% to 100%, positive predictive value of 25% to 85%, negative predictive value of 96% to 100%, and balanced accuracy of 53% to 100%) than the other two CPA methods. When the CPA methods were applied to reports of syncope or dizziness following human papillomavirus (HPV) immunization in the KAERS database, Taylor-CPA and EnvCpt detected a change point (Q2/2013), which was consistent with actual public safety concerns. CPA can be applied as an efficient tool for the early detection of vaccine safety signals. Full article

Sexual and gender minority (SGM) populations are particularly vulnerable to poor COVID-19 outcomes and are more likely to experience stigma and medical mistrust that may impact COVID-19 vaccine acceptance. This study examined the prevalence of COVID testing and diagnosis and assessed COVID-19 vaccine acceptance among a large sample of SGM. Participants were recruited as part of an online cross-sectional study focused on an HIV biomedical prevention technology willingness in the United States at increased risk for HIV sero-conversion. Multivariate linear analysis was conducted to examine COVID-19 vaccine acceptance. The study sample included 1350 predominately gay (61.6%), Black (57.9%), cis-gender (95.7%) males with a mean age of 32.9 years. Medical mistrust and social concern regarding COVID-19 vaccine stigma were significantly associated with decreased COVID-19 vaccine acceptance, and altruism was significantly associated with increased vaccine acceptance. Black participants were significantly less likely to accept a COVID-19 vaccine, and Asian participants were significantly more likely to accept a vaccine, compared to White peers. As the planning of COVID-19 vaccine rollout efforts is conceptualized and designed, these data may inform equitable implementation strategies and prevent worsening health inequities among SGM populations. Full article

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol. Full article

The mean age of lung transplant recipients has significantly increased in recent decades. Elderly recipients have a higher risk of developing herpes zoster (HZ), and they have in general a worse response to vaccination than younger persons do. We investigated the relationship between the humoral and cellular immune response to a live-attenuated HZ vaccine (Zostavax^®, Merck Sharp and Dohme) and the frequencies of T and B cell subsets, especially aged cell subsets (CD28−T cells and age associated B cells, ABCs). In total, 37 patients awaiting lung transplantation received one dose of Zostavax^®, and peripheral blood was collected before and within 6 months after vaccination. We observed a robust immune response after vaccination. The frequencies of CD28−T cells before vaccination had no impact on the subsequent immune response to HZ vaccination. However, a higher frequency of ABCs before vaccination correlated with a lower immune response especially regarding the cellular immune response. Cytomegalovirus seropositivity was associated with increased frequencies of CD28−T cells but not with frequencies of ABCs in the patients. In conclusion, increased levels of ABCs might disturb the cellular immune response to HZ vaccination, which could lower the efficacy of such vaccination in elderly transplant recipients. Full article

Access to vaccination information could influence public attitudes towards vaccination. This study investigated the number and types of vaccination-related information sources, and estimated their associations with vaccine confidence and hesitancy in China. In January 2019, we conducted a cross-sectional survey in China, and 2122 caregivers with children <6 years completed self-administered questionnaires. Logistic regressions were used to assess associations between caregivers’ primary information sources and vaccine confidence/hesitancy. A majority (72%) of caregivers had multiple sources of vaccination-related information. The proportions of caregivers reporting professional sources, media, and peers as primary information sources were 81%, 63%, and 26%. Internal migrants were less likely to get information from professional sources; more educated and wealthier caregivers reported more information sources and were more likely to get information from media and peers. Caregivers who reported professional information sources had significantly higher odds of being confident about the safety of vaccines and lower odds of being hesitant toward vaccination than those who did not. Caregivers who reported the media as a primary information source had significantly higher odds of being hesitant toward vaccination than those who did not. To address vaccine hesitancy, it is essential to promote universal access to professional vaccination-related information sources, and to use the media to disseminate evidence-based information and clarify misinformation. Health communication should target internal migrants, and more educated and wealthier caregivers. Full article

Health Care Workers are at the front line of the fight against Covid-19. The aim of this study was to evaluate the acceptability of vaccination against COVID-19 among health professionals (physicians, dentists, pharmacists) two weeks prior to the start of the Greek vaccination campaign against COVID-19. A cross-sectional online survey was conducted over the period 15–22 December 2020 in 340 health professionals in Central Greece. We found a high level of acceptance for COVID-19 vaccine (78.5%) and a high vaccination coverage for the influenza vaccine (74%). Age > 45 years (OR = 2.01; 95% C.I. = 2.01−4.3), absence of fear over vaccine safety (OR = 4.09; 95% C.I. = 1.36–12.3), and information received from the Greek public health authorities (OR = 11.14; 95% C.I. = 5.48–22.6), were factors independently associated with the likelihood of COVID-19 vaccination acceptance. Our study indicates a high level of the COVID-19 vaccination acceptance among physicians, dentists and pharmacists. Nevertheless, several interventions can be implemented to increase acceptance of vaccine among health-care workers (HCWs) and could be especially directed at younger and vaccine-hesitant health care workers due to fear of vaccine side-effects. Last, our results provide some evidence that receiving vaccine-related information from the Greek Center for Diseases Control (E.O.D.Y.) could reduce the drivers of hesitancy and enhance the acceptability of COVID-19 vaccination. Full article

Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) and herpangina. Moreover, EV-A71 infection can lead to neurological complications and death. Vaccination is the most efficient way to control virus infection. There are currently three inactivated, whole EV-A71 vaccines licensed by the China NMPA (National Medical Products Administration). Several other types of vaccines, such as virus-like particles and recombinant VP1 (capsid protein), are also under development. In this review, we discuss recent advances in the development of EV-A71 vaccines. Full article

Humanized mice are critical for HIV-1 research, but humanized mice generated from cord blood are inefficient at mucosal HIV-1 transmission. Most mucosal HIV-1 transmission studies in mice require fetal tissue-engraftment, the use of which is highly restricted or prohibited. We present a fetal tissue-independent model called CD34T+ with enhanced human leukocyte levels in the blood and improved T cell homing to the gut-associated lymphoid tissue. CD34T+ mice are highly permissive to intra-rectal HIV-1 infection and also show normal env diversification in vivo despite high viral replication. Moreover, mucosal infection in CD34T+ mice can be prevented by infusion of broadly neutralizing antibodies. CD34T+ mice can be rapidly and easily generated using only cord blood cells and do not require any complicated surgical procedures for the humanization process. Therefore, CD34T+ mice provide a novel platform for mucosal HIV-1 transmission studies as well as rapid in vivo testing of novel prevention molecules against HIV-1. Full article