Vaccines

Following a successful Human Papilloma Virus (HPV) vaccination pilot in 2013–2015 in Kitui county, Kenya introduced the HPV vaccine in October 2019 with a goal to immunize approximately 800,000 girls annually against HPV. Our study assessed the knowledge, attitudes, and practice of affected groups towards HPV infection and vaccination in two counties of Kenya. Semi-structured interviews from children aged between nine and thirteen years and key informants comprising of parents, head teachers, community leaders and health workers involved in HPV vaccination in health facilities from Mombasa and Tana-River counties were conducted. Content was analyzed thematically and coded for emerging themes using the QRS Nvivo 12 Plus software package. From our findings, a significant proportion of participants, especially children, have limited knowledge of the subject. Vaccination of boys was opposed by most participants. Parents and the community members are not in favor of HPV vaccination, as compared to the other groups. A similar pattern of inadequate knowledge and strongly opposed attitudes was observed in Tana-River and Mombasa. Active community involvement in primary prevention strategies may promote the uptake of the vaccine which can be achieved by robust awareness, modifying the negative beliefs about HPV vaccine and encouraging the perceptibility of HPV vaccination. Full article

Tuberculosis (TB) is the leading cause of death of any single infectious agent, having led to 1.4 million deaths in 2019 alone. Moreover, an estimated one-quarter of the global population is latently infected with Mycobacterium tuberculosis (MTB), presenting a huge pool of potential future disease. Nonetheless, the only currently licensed TB vaccine fails to prevent the activation of latent TB infections (LTBI). These facts together illustrate the desperate need for a more effective TB vaccine strategy that can prevent both primary infection and the activation of LTBI. In this study, we employed a machine learning-based reverse vaccinology approach to predict the likelihood that each protein within the proteome of MTB laboratory reference strain H37Rv would be a protective antigen (PAg). The proteins predicted most likely to be a PAg were assessed for their belonging to a protein family of previously established PAgs, the relevance of their biological processes to MTB virulence and latency, and finally the immunogenic potential that they may provide in terms of the number of promiscuous epitopes within each. This study led to the identification of 16 proteins with the greatest vaccine potential for further in vitro and in vivo studies. It also demonstrates the value of computational methods in vaccine development. Full article

COVID-19 has been spreading worldwide since late 2019. There is no definitive cure to date. Global vaccination programs are urgently required to confer herd immunity, reducing the incidence of COVID-19 infections and associated morbidity and mortality. However, a significant proportion of special populations are hesitant to receive vaccination due to their special conditions, namely, age (pediatrics and geriatrics), immunocompromised state, autoimmune diseases, chronic cardiovascular and pulmonary conditions, active or treated cancers, and pregnancy. This review aims to evaluate the existing evidence of COVID-19 vaccinations on these special populations and to provide clues to guide vaccination decision making to balance the benefits and risks of vaccinations. Full article

As worldwide large-scale inoculation of novel vaccines is on the way, the importance of real-world data on safety cannot be overemphasized. We aimed to investigate the adverse events following immunization (AEFIs) associated with the ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs). We investigated the systemic and local adverse events reported within seven days following the first and second doses of vaccination, using the mobile vaccine adverse events reporting system (MVAERS) developed by our hospital. The response rates were 71.8% (994/1384) and 52.9% (727/1375) after the first and second doses, respectively. The most commonly reported AEFIs were tenderness and pain at the injection site and fatigue after the first and second doses. In comparison to the first dose, the incidence and severity of AEFIs were lower following the second dose. Since the Korean government does not recommend the ChAdOx1 nCoV-19 vaccination for those under 30 years of age, with greater risk than benefit, we additionally compared the AEFIs of age groups under and above 30 years of age. The overall incidence of AEFIs was similar in both the under and over 30 age groups. In conclusion, AEFIs associated with the ChAdOx1 nCoV-19 vaccine were found to be tolerable, and AEFIs associated with the second dose were less common and severe compared to the first dose. Further safety surveillance studies on COVID-19 vaccines are required to validate our findings. Full article

Mutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process partly explain the suboptimal effectiveness of traditional seasonal influenza vaccines. Cell-based influenza vaccines improve antigenic match and vaccine effectiveness by avoiding such egg-adaptation. This study evaluated the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adults (18–64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe) in the US. The impact of QIVc over QIVe in public health and cost outcomes was estimated using a dynamic age-structured SEIR transmission model, which accounted for four circulating influenza strains [A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)] and was calibrated on the 2013–2018 influenza seasons. The robustness of the results was assessed in univariate and probabilistic sensitivity analyses. Switching from QIVe to QIVc in 18- to 64-year-olds may prevent 5.7 million symptomatic cases, 1.8 million outpatient visits, 50,000 hospitalizations, and 5453 deaths annually. The switch could save 128,000 Quality-Adjusted Life Years (QALYs) and US $ 845 M in direct costs, resulting in cost-savings in a three-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result. The analysis shows that QIVc is expected to prevent hospitalizations and deaths, and result in substantial savings in healthcare costs. Full article

Influenza vaccine uptake in India is poor, and scant data exist regarding the effectiveness of influenza vaccine against hospitalization. Methods: From October 2019 to March 2020, vaccination status of 1219 patients (males n = 571, aged 5–107 years; median, 50 years) hospitalized with severe acute respiratory illness (SARI) was assessed. The patients were tested for influenza viruses and their subtypes by RT PCR. Sequencing of the HA gene was performed. Vaccine effectiveness (VE) against influenza subtypes was estimated by the test negative design. Results: A total of 336 (27.5%) patients were influenza-positive, with influenza B/Victoria accounting for 49.7% (n = 167), followed by influenza A/H1N1 (47.6%; n = 155) and influenza A/H3N2 (4.4%; n = 15). About 6.8% and 8.6% of the influenza-positive and influenza-negative patients, respectively, had been vaccinated. Adjusted VE for any influenza strain was 13% (95% CI −42 to 47), which for influenza B was 0%. HA sequencing revealed that influenza B samples mainly belonged to subclade V1A.3/133R with deletion of residues 163–165, as against the 2-aa deletion in influenza B/Colorado/06/2017 strain, contained in the vaccine. VE for influenza A/H1N1 was 55%. Conclusions: Poor VE due to a genetic mismatch between the circulating strain and the vaccine strain calls for efforts to reduce the mismatch. Full article

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8⁺ T cell immunity to wide range of epitopes, could help translational efforts to improve coronavirus disease 2019 (COVID-19) prevention and therapy. However, there have been few direct studies in which such immunity exists in a population. Methods: We selected SARS-CoV-2-conserved structural peptides that are not prone to mutation as antigens for broad-spectrum CD8⁺ T cell immunity. Peripheral blood mononuclear cells (PBMCs) from unexposed healthy donors were stimulated with these peptides in vitro and CD8⁺ T cell-specific response was monitored. The conserved peptide-specific CD8⁺ T cells were sorted for T cell receptor (TCR) repertoire sequencing. The presence of specific complementary determining region 3 (CDR3) clones was analyzed in a healthy cohort. Results: For each structural protein, including S, E, M, N, the conserved peptides could potentially provide the largest number of major histocompatibility complex-I (MHC-I) epitopes in the Oriental and Caucasian populations. For conserved peptides from spike (S), envelope (E), membrane (M), nucleocapsid (N) proteins, we found that there were no cross-reactive memory T cells in the unexposed individuals. Instead, their T cells contain naïve TCR repertoire recognizing these conserved peptides. Using TCR sequencing and CDR3 clustering for the conserved peptides specific T cells, we found that the recovered patients had a higher proportion of TCR repertoire similar with that of specific CD8⁺ T cells in unexposed individuals. Meanwhile, CDR3 clones of the above T cells were widely present in the healthy population. Conclusions: This study provides evidence of broad-spectrum SARS-CoV-2 specific CD8⁺ TCR repertoire in unexposed healthy population, which is implicated in the development and implementation of broad-spectrum vaccines against COVID-19. Full article

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (−55.4% with total antibody assay; −89.6% with IgG assay) and seropositive individuals (−74.8% with total antibody assay; −79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13–65) in seronegative and 53 days (95% CI: 40–79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54–90) to 114 days (95% CI: 87–167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (−98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies. Full article

Foot-and-mouth disease (FMD) is a notifiable contagious disease of cloven-hoofed mammals. A high potency vaccine that stimulates the host immune response is the foremost strategy used to prevent disease persistence in endemic regions. FMD vaccines comprise inactivated virus antigens whose immunogenicity is potentiated by immunogenic adjuvants. Oil-based adjuvants have clear advantages over traditional adjuvant vaccines; however, there is potential to develop novel adjuvants to increase the potency of FMD vaccines. Thus, we aimed to evaluate the efficacy of a novel water-in-oil emulsion, called CAvant^®SOE, as a novel vaccine adjuvant for use with inactivated FMD vaccines. In this study, we found that inactivated A22 Iraq virus plus CAvant^®SOE (iA22 Iraq-CAvant^®SOE) induced effective antigen-specific humoral (IgG, IgG1, and IgG2a) and cell-mediated immune responses (IFN-γ and IL-4) in mice. Immunization of pigs with a single dose of iA22 Iraq-CAvant^®SOE also elicited effective protection, with no detectable clinical symptoms against challenge with heterologous A/SKR/GP/2018 FMDV. Levels of protection are strongly in line with vaccine-induced neutralizing antibody titers. Collectively, these results indicate that CAvant^®SOE-adjuvanted vaccine is a promising candidate for control of FMD in pigs. Full article

Background: The Oxford–AstraZeneca vaccine (Covishield) was the first to be introduced in Bangladesh to fight the ongoing global COVID-19 pandemic. As this vaccine had shown some side-effects in its clinical trial, we aimed to conduct a study assessing short-term adverse events following immunization (AEFIs) in Bangladesh. Method: A cross-sectional study was conducted on social and electronic media platforms by delivering an online questionnaire among people who had taken at least one dose of the COVID-19 vaccine. The collected data were then analysed to evaluate various parameters related to the AEFIs of the respondents. Results: A total of 626 responses were collected. Of these, 623 were selected based on complete answers and used for the analysis. Most of the respondents were between 30–60 years of age, and 40.4% were female. We found that a total of 8.5% of the total respondents had been infected with the SARS-CoV-2 virus. Our survey revealed that out of 623 volunteers, 317 reported various side-effects after taking the vaccine, which is about 50.88% of the total participants. The majority of participants (37.07%, 231/623) reported swelling and pain at the injection site and fever (25.84%, 162/623); these were some of the common localized and generalized symptoms after the COVID-19 vaccine administration. Conclusion: The side-effects reported after receiving the Oxford–AstraZeneca vaccine (Covishield) are similar to those reported in clinical trials, demonstrating that the vaccines have a safe therapeutic window. Moreover, further research is needed to determine the efficacy of existing vaccines in preventing SARS-CoV-2 infections or after-infection hospitalization. Full article

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe—defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958–26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; p < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC₅₀) median 769 versus 485; p < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response. Full article

China has initiated the COVID-19 vaccination for children aged 15–17 years since late July 2020. This study aimed to determine the association between adult vaccine hesitancy and parental acceptance of childhood COVID-19 vaccines in a multi-ethnicity area of northwestern China. A web-based investigation was performed with a convenience sampling strategy to recruit the parents aged 20–49 years. In a total of 13,451 valid respondents, 66.1% had received the COVID-19 vaccination, 26.6% were intent to receive, while 7.3% were not intent, with an increasing vaccine hesitancy (p < 0.001). Moreover, vaccination uptake of four common vaccines in their children remained low (29.0% for influenza vaccine, 17.9% for pneumonia vaccine, 10.9% for rotavirus vaccine, 8.0% for Enterovirus-71 vaccine), while overall parental acceptance of childhood COVID-19 vaccines was 50.0% (32.7% for those aged 0–5, 46.6% for 6–10, 73.3% for 11–18; p < 0.001). Vaccination uptake of these four vaccines and parental acceptance of childhood COVID-19 vaccine were negatively associated with adult vaccine hesitancy. In addition, respondents mostly preferred childhood COVID-19 vaccines with weak mild common adverse events (β = 1.993) and no severe adverse events (β = 1.731), demonstrating a positive association with adult vaccine hesitancy. Thus, it warrants specific countermeasures to reduce adult vaccine hesitancy and improve strategies for childhood vaccination. Full article

Klebsiella is a genus of nosocomial bacterial pathogens and is placed in the most critical list of World Health Organization (WHO) for development of novel therapeutics. The pathogens of the genus are associated with high mortality and morbidity. Owing to their strong resistance profile against different classes of antibiotics and nonavailability of a licensed vaccine, urgent efforts are required to develop a novel vaccine candidate that can tackle all pathogenic species of the Klebsiella genus. The present study aims to design a broad-spectrum vaccine against all species of the Klebsiella genus with objectives to identify the core proteome of pathogen species, prioritize potential core vaccine proteins, analyze immunoinformatics of the vaccine proteins, construct a multi-epitopes vaccine, and provide its biophysical analysis. Herein, we investigated all reference species of the genus to reveal their core proteome. The core proteins were then subjected to multiple reverse vaccinology checks that are mandatory for the prioritization of potential vaccine candidates. Two proteins (TonB-dependent siderophore receptor and siderophore enterobactin receptor FepA) were found to fulfill all vaccine parameters. Both these proteins harbor several potent B-cell-derived T-cell epitopes that are antigenic, nonallergic, nontoxic, virulent, water soluble, IFN-γ producer, and efficient binder of DRB*0101 allele. The selected epitopes were modeled into a multi-epitope peptide comprising linkers and Cholera Toxin B adjuvant. For docking with innate immune and MHC receptors and afterward molecular dynamics simulations and binding free energy analysis, the vaccine structure was modeled for tertiary structure and refined for structural errors. To assess the binding affinity and presentation of the designed vaccine construct, binding mode and interactions analysis were performed using molecular docking and molecular dynamics simulation techniques. These biophysical approaches illustrated the vaccine as a good binder to the immune receptors and revealed robust interactions energies. The vaccine sequence was further translated to nucleotide sequence and cloned into an appropriate vector for expressing it at high rate in Escherichia coli K12 strain. In addition, the vaccine was illustrated to generate a good level of primary, secondary, and tertiary immune responses, proving good immunogenicity of the vaccine. Based on the reported results, the vaccine can be a good candidate to be evaluated for effectiveness in wet laboratory validation studies. Full article

First detected in Wuhan, China, a highly contagious coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19, spread globally in December of 2019. As of 19 September 2021, approximately 4.5 million people have died globally, and 215 million active cases have been reported. To date, six vaccines have been developed and approved for human use. However, current production and supply capabilities are unable to meet global demands to immunize the entire world population. Only a few countries have been able to successfully vaccinate many of their residents. Therefore, an alternative vaccine that can be prepared in an easy and cost-effective manner is urgently needed. A vaccine that could be prepared in this manner, as well as can be preserved and transported at room temperature, would be of great benefit to public health. It is possible to develop such an alternative vaccine by using nano- or microparticle platforms. These platforms address most of the existing vaccine limitations as they are stable at room temperature, are inexpensive to produce and distribute, can be administered orally, and do not require cold chain storage for transportation or preservation. Particulate vaccines can be administered as either oral solutions or in sublingual or buccal film dosage forms. Besides improved patient compliance, the major advantage of oral, sublingual, and buccal routes of administration is that they can elicit mucosal immunity. Mucosal immunity, along with systemic immunity, can be a strong defense against SARS-CoV-2 as the virus enters the system through inhalation or saliva. This review discusses the possibility to produce a particulate COVID vaccine by using nano- or microparticles as platforms for oral administration or in sublingual or buccal film dosage forms in order to accelerate global vaccination. Full article

Lack of understanding of the immune response to mycobacterial pathogens has impeded progress in development of vaccines. Infection leads to development of an immune response that controls infection but is unable to eliminate the pathogen, resulting in a persistent infection. Although this puzzle remains to be solved, progress has been made using cattle as a model species to study the immune response to a prototypic mycobacterium, Mycobacterium a. paratuberculosis (Map). As chronicled in the review, incremental advances in characterizing the immune response to mycobacteria during the last 30 years with increases in information on the evolution of mycobacteria and relA, a gene regulating the stringent response, have brought us closer to an answer. We provide a brief overview of how mycobacterial pathogens were introduced into cattle during the transition of humankind to nomadic pastoralists who domesticated animals for food and farming. We summarize what is known about speciation of mycobacteria since the discovery of Mybacterium tuberculsis Mtb, M. bovis Mbv, and Map as zoonotic pathogens and discuss the challenges inherent in the development of vaccines to mycobacteria. We then describe how cattle were used to characterize the immune response to a prototypic mycobacterial pathogen and development of novel candidate vaccines. Full article

Porcine epidemic diarrhea (PED), which is caused by the porcine epidemic diarrhea virus (PEDV), has occurred worldwide and poses a serious threat to the pig industry. Intestine is the main function site of PEDV; therefore, it is important to develop an oral mucosal immunity vaccine against this virus infection. Most traditional plasmid delivery vectors use antibiotic genes as a selective marker, easily leading to antibiotic accumulation and gene contamination. In this study, to explore whether the alanine racemase gene (Alr) could be used as a screening marker and develop an efficient oral vaccine against PEDV infection, a recombinant strain was constructed using Lactobacillus casei with Alr deletion (L. casei ΔAlr W56) to deliver the Alr gene and a core-neutralizing epitope (COE) antigen. This recombinant bacterium efficiently induced secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in mice. Compared to the other strains, the recombinant bacteria were able to grow without the addition of D-alanine, revealing that Alr in the plasmid could function normally in defective bacteria. This oral mucosal vaccine would provide a useful strategy to substitute the application of antibiotics in the future and induce efficient immune responses against PEDV infection. Full article

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates, and other susceptible animals have been involved in the study of COVID-19. Moreover, 117 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines, and messenger ribonucleic acid (mRNA) vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models for COVID-19 vaccine evaluation and advanced vaccines with an efficacy range from about 50% to more than 95%. In addition, we point out future directions for COVID-19 animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2. Full article

The combination of primary and secondary prevention has already influenced the colposcopic practice by reduction in HPV (human papillomavirus) vaccine-type HSIL (HIGH-GRADE SIL), colposcopy referral numbers, colposcopic positive predictive value (PPV) for CIN2+, and by modification of referral pattern, colposcopic performance, and procedures. Different strategies, both isolated and combined, have been proposed in order to maintain the diagnostic accuracy of colposcopy: patient risk stratification based on immediate or future risk of CIN3+ or on HPV genotyping after a positive screening test. Data are needed to support alternative colposcopic strategies based on vaccination status and on the application of artificial intelligence where the patient’s risk stratification is implicit in precision medicine which involves the transition from an operator-dependent morphology-based to a less-operator dependent, more biomolecular management. The patient’s risk stratification based on any combination of “history” and “test results” to decrease colposcopy workload further reduce colposcopic and histologic morphological approaches, while adding genotyping to the risk stratification paradigm means less cytologic morphologic diagnosis. In Italy, there is a strong colposcopic tradition and there is currently no immediate need to reduce the number of colposcopies. Instead, there is a need for more accredited colposcopists to maintain the diagnostic accuracy of colposcopy in the vaccination era. Full article