Effectiveness Of Current Vaccines Research Articles

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

COVID-19 Vaccine Acceptance and Hesitancy among Migrants, Refugees, and Foreign Workers: A Systematic Review and Meta-Analysis.

Despite the effectiveness of current vaccines in reducing the spread and severity of SARS-CoV-2 infections, many people, including migrants, refugees, and foreign workers, are hesitant to be vaccinated. This systematic review and meta-analysis (SRMA) was conducted to determine the pooled prevalence estimate of the acceptance and hesitancy rates of the COVID-19 vaccine among these populations. A comprehensive search of the peer-reviewed literature indexed in PubMed, Scopus, Science Direct, and Web of Science databases was conducted. Initially, 797 potential records were identified, of which 19 articles met the inclusion criteria. A meta-analysis of proportions using data from 14 studies revealed that the overall acceptance rate of COVID vaccination among 29,152 subjects was 56.7% (95% CI: 44.9-68.5%), while the prevalence of vaccine hesitancy among 26,154 migrants reported in 12 studies was estimated to be 31.7% (95% CI: 44.9-68.5%). The acceptance rate for the COVID-19 vaccination first declined from 77.3% in 2020 to 52.9% in 2021 and then slightly increased to 56.1% in 2022. The most frequent factors influencing vaccine hesitancy were worries about vaccine efficacy and safety. Intensive vaccination campaigns should be implemented to raise vaccination awareness among migrants, which will increase the acceptance rate for the COVID-19 vaccine and result in herd immunity.

Impact of prior SARS-COV-2 infection and vaccination on COVID-19 hospital admission and mortality amongst nursing home residents.

Nursing home residents (NHRs) have experienced disproportionately high risk of severe outcomes due to COVID-19 infection. We investigated the impact of COVID-19 vaccinations and previous SARS-CoV-2 episodes in preventing hospitalization and mortality in NHRs. Retrospective study of a cohort of all NHRs in our area who were alive at the start of the vaccination campaign. The first three doses of SARS-CoV-2 vaccine and prior COVID-19 infections were registered. The main outcomes were hospital admission and mortality during each follow up. Random effects time-varying Cox models adjusted for age, sex, and comorbidities were fitted to estimate hazard ratios (HRs) according to vaccination status. COVID-19 hospitalization and death rates for unvaccinated NHRs were respectively 2.39 and 1.42 per 10,000 person-days, falling after administration of the second dose (0.37 and 0.34) and rising with the third dose (1.08 and 0.8). Rates were much lower amongst people who had previously had COVID-19. Adjusted HRs indicated a significant decrease in hospital admission amongst those with a two- and three-dose status; those who had had a previous COVID-19 infection had even lower hospital admission rates. Death rates decreased as NHRs received two and three doses, and the probability of death was much lower among those who had previously had the infection. The effectiveness of current vaccines against severe COVID-19 disease in NHRs remains high and SARS-CoV-2 episodes prior to vaccination entail a major reduction in hospitalization and mortality rates. The protection conferred by vaccines appears to decline in the following months. ClinicalTrials.gov Identifier: NCT04463706.

Historical review of vaccination against meningococcus in Spain (1996–2021). Learned lessons

Invasive meningococcal disease (IMD) is a major cause of morbidity and mortality, primarily affecting infants and adolescents. The progressive development of vaccines in the last 25 years has allowed a preventive approach to the disease through different strategies based on epidemiological changes and the availability of vaccine preparations. This paper is a historical review of the different immunoprevention strategies and their impact against EMI established between 1996 and 2021 in Spain. Currently, only vaccines have demonstrated the ability to prevent this disease. In line with the objectives established by the World Health Organisation (WHO) in the initiative “Defeat meningitis in the year 2030” and based on the evidence of the impact and effectiveness of current vaccines, it is necessary to incorporate new preventive measures against invasive meningococcal disease, especially in the age cohorts with the highest incidence, such as infants and adolescents.

Impacts of delta and omicron variants on inactivated SARS‐CoV‐2 vaccine‐induced T cell responses in patients with autoimmune diseases and healthy controls

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), which is still devastating economies and communities globally. The increasing infections of variants of concern (VOCs) in vaccinated population have raised concerns about the effectiveness of current vaccines. Patients with autoimmune diseases (PAD) under immunosuppressant treatments are facing higher risk of infection and potentially lower immune responses to SARS-CoV-2 vaccination. Blood samples were collected from PAD or healthy controls (HC) who finished two or three doses of inactivated vaccines. Spike peptides derived from wild-type strain, delta, omicron BA.1 were utilisedto evaluate T cell responses and their cross-recognition of delta and omicron in HC and PAD by flow cytometry and ex vivo IFNγ-ELISpot. We found that inactivated vaccine-induced spike-specific memory T cells were long-lasting in both PAD and HC. These spike-specific T cells were highly conserved and cross-recognized delta and omicron. Moreover, a third inactivated vaccine expanded spike-specific T cells that responded to delta and omicron spike peptides substantially in both PAD and HC. Importantly, the polyfunctionality of spike-specific memory T cells was preserved in terms of cytokine and cytotoxic responses. Although the extent of T cell responses was lower in PAD after two-dose, T cell responses were boosted to a greater magnitude in PAD by the third dose, bringing comparable spike-specific T cell immunity after the third dose. Inactivated vaccine-induced spike-specific T cells remain largely intact against delta and omicron variants. This study expands our understanding of inactivated vaccine-induced T cell responses in PAD and HC, which could have important indications for vaccination strategy.

Revisión histórica de la vacunación frente a meningococo en España (1996-2021). Lecciones aprendidas

Invasive meningococcal disease is a major cause of morbidity and mortality, primarily affecting infants and adolescents. The progressive development of vaccines in the last 25 years has allowed a preventive approach to the disease through different strategies based on epidemiological changes and the availability of vaccine preparations. This paper is a historical review of the different immunoprevention strategies and their impact against EMI established between 1996 and 2021 in Spain. Currently, only vaccines have demonstrated the ability to prevent this disease. In line with the objectives established by the World Health Organization in the initiative «Defeat meningitis in the year 2030» and based on the evidence of the impact and effectiveness of current vaccines, it is necessary to incorporate new preventive measures against invasive meningococcal disease, especially in the age cohorts with the highest incidence, such as infants and adolescents.

Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants.

Is the Omicron variant of SARS-CoV-2 coming to an end?

Is the Omicron variant of SARS-CoV-2 coming to an end?

Identification, propagation and molecular characterization of SARS-CoV-2 delta variant isolated from Egyptian COVID-19 patients

The recently emerging coronavirus, severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2) is the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic. Since its discovery in the city of Wahan, China, SARS-CoV-2 has spread rapidly to invade all countries. In addition to its rapid transmission rate, it is characterized by high genetic mutation rates. The aim of this study is to provide an effective method for the isolation and propagation of SARS-CoV-2 in cell lines without any induction of genetic variations. In this study, we isolated SARS-CoV-2 from oro-nasopharyngeal swabs collected from Egyptian patients who were clinically diagnosed with COVID-19. Molecular identification of SARS-CoV-2 was performed by Real-Time Quantitative Reverse Transcription PCR (RT-qPCR). The isolated virus was propagated on Vero E6 cells without applying serial viral passages to avoid any variation of the viral genome. The replication and propagation were confirmed by the results of both RT-qPCR and the cytopathic effect (CPE). Moreover, SARS-CoV-2 was completely inactivated chemically using beta-propiolactone (βPL). Whole genome sequencing (WGS) of the propagated virus was performed in order to investigate mutational patterns. The genome sequences recovered in 2020 (n = 18) were similar to the reference strain, Wuhan-Hu-1, and were clustered as clade 20A. However, the genomic sequences recovered in 2021 (n = 2) were clustered as clade 21J. These two sequences are considered the first Delta (B.1.617.2) variants detected in Egypt. This study provides a reference for researchers in Egypt to isolate and propagate SARS-CoV-2 easily and efficiently. Furthermore, the prevalence of the SARS-CoV-2 delta variant in Egypt necessitates continuous monitoring of the efficacy of the applied treatment protocol and the effectiveness of current vaccines against such variants of concern (VOC).

Progress towards the Elusive Mastitis Vaccines.

Mastitis is a major problem in dairy farming. Vaccine prevention of mammary bacterial infections is of particular interest in helping to deal with this issue, all the more so as antibacterial drug inputs in dairy farms must be reduced. Unfortunately, the effectiveness of current vaccines is not satisfactory. In this review, we examine the possible reasons for the current shortcomings of mastitis vaccines. Some reasons stem from the peculiarities of the mammary gland immunobiology, others from the pathogens adapted to the mammary gland niche. Infection does not induce sterilizing protection, and recurrence is common. Efficacious vaccines will have to elicit immune mechanisms different from and more effective than those induced by infection. We propose focusing our research on a few points pertaining to either the current immune knowledge or vaccinology approaches to get out of the current deadlock. A possible solution is to focus on the contribution of cell-mediated immunity to udder protection based on the interactions of T cells with the mammary epithelium. On the vaccinology side, studies on the orientation of the immune response by adjuvants, the route of vaccine administration and the delivery systems are among the keys to success.

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults.

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND50) titers in serum samples. ND50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0–12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7–294.0]) and delta (24.3 [14.3–81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.

Emergence of the First Strains of SARS-CoV-2 Lineage B.1.1.7 in Romania: Genomic Analysis.

BackgroundThe United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant (B.1.1.7) that rapidly spread to other countries. The impact of this new mutation—which occurs in the S protein—on infectivity, virulence, and current vaccine effectiveness is still under evaluation.ObjectiveThe aim of this study is to sequence SARS-CoV-2 samples of cases in Romania to detect the B.1.1.7 variant and compare these samples with sequences submitted to GISAID.MethodsSARS-CoV-2 samples were sequenced and amino acid substitution analysis was performed using the CoV-GLUE platform.ResultsWe have identified the first cases of the B.1.1.7 variant in samples collected from Romanian patients, of which one was traced to the region of the United Kingdom where the new variant was originally sequenced. Mutations in nonstructural protein 3 (Nsp3; N844S and D455N) and ORF3a (L15F) were also detected, indicating common ancestry with UK strains as well as remote connections with strains from Nagasaki, Japan.ConclusionsThese results indicate, for the first time, the presence and characteristics of the new variant B.1.1.7 in Romania and underscore the need for increased genomic sequencing in patients with confirmed COVID-19.

New and Newer Vaccines for SARS-CoV-2 Variants. Are the Major Vaccine Developers on the Right Track, Or Is Delipidation the Answer?

Background: Global Covid-19 pandemic has led to remarkable scientific achievements resulting in the development and rapid implementation of vaccines towards the original wild-type SARS-CoV-2 virus. Most Covid-19 vaccines are targeted to only one protein (the Spike protein) on the virus. SARS-CoV-2 that causes Covid-19 naturally undergoes multiple mutations over time. Such mutations can be inconsequential or have dire consequences. The lack of effectiveness of current vaccines towards mutated variants of Covid-19 is of major concern. The objective of this study is to describe an optimal solvent system that creates, via delipidation, a non-synthetic, host-derived or nonhost-derived modified viral particle that has its lipid envelope removed, exposing hidden undenatured proteins from within the virus, that generate a positive immunologic response when administered into a host, thereby providing a vaccine that offers strong and broad protection against the virus. Methods: Lipid removal from viruses by specific procedures renders the exposure of hidden proteins. Protection by antibodies to all of the virus’ protein types has shown to be far superior to protection by antibodies that are created by a single protein type. Results: Published studies with the Hepatitis virus, Pestivirus and HIV virus have reported the wide range of applications with this delipidation approach resulting in effectively long-term and broad protection vaccines. Conclusion: Mutations are rendering existing vaccines less effective. New approaches to obtain a more permanent vaccine that minimizes the effects of mutation are obtainable by delipidation of the viral particle and thereby creating vaccines that are more permanent with broad protection.

Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus.

Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity. Therefore, a number of approaches have been developed to target specific PRRs in an effort to stimulate innate immunity and reduce disease in a variety of settings, including during influenza infections. Herein, we discuss progress in immunomodulation strategies designed to target cell-associated PRRs of the innate immune system, thereby, modifying innate responses to IAV infection and/or augmenting immune responses to influenza vaccines.

Protection against lethal vaccinia virus infection in mice using an siRNA targeting the A5R gene.

Although the World Health Organization has declared the eradication of smallpox in 1980, the fear of its potential use in bioterrorism has become a reality. Since the effectiveness of current vaccines and antiviral drugs is limited, development of new therapeutic strategies is needed. In this study, we investigated small interfering RNA (siRNA) as a therapeutic approach for preventing and treating smallpox infection. Eight siRNA sequences were designed and evaluated for antiviral activity against vaccinia virus (VACV) in vitro and in vivo. Of eight siRNAs, A5R1 siRNA targeted the A5R gene and reduced VACV replication in cell culture by up to 85% at 100 nM concentration without inducing cytotoxicity. A prolonged prophylactic as well as therapeutic effect of siRNA was observed. In addition, real-time PCR analysis showed that A5R1 siRNA can especially reduce the target mRNA. Finally, intraperitoneal delivery of A5R1 siRNA in Balb/c mice significantly protected these animals from lethal challenge with VACV. This study suggests the potential of A5R1 siRNA as a therapeutic antiviral agent against smallpox.

Pneumococcal Infections in HIV Infected Adults - Clinical Features, Reasons behind the Association and Future Hopes for Prevention

Streptococcus pneumoniae is the most important bacterial cause of pneumonia and meningitis among adults world wide. It is a particularly common cause of these infections and also bacteraemia among HIV infected adults with rates of disease increasing to more than 100 times the normal as HIV infection progresses to AIDS. This article briefly describes the common presentations and outcomes of pneumococcal disease (PD) in HIV infected adult inpatients in Malawi. Factors underlying susceptibility to pneumococcal infection in HIV infected adults are then reviewed, along with the effectiveness of current vaccines. Finally, novel approaches that will be needed to combat PD in HIV afflicted parts of the world are suggested.

European bat lyssaviruses: an emerging zoonosis.

In Europe, two bat lyssaviruses referred to as European bat lyssaviruses (EBLVs) types 1 and 2 (genotypes 5 and 6 respectively) which are closely related to classical rabies virus are responsible for an emerging zoonosis. EBLVs are host restricted to bats, and have been known to infect not only their primary hosts but also in rare circumstances, induce spillover infections to terrestrial mammals including domestic livestock, wildlife and man. Although spillover infections have occurred, there has been no evidence that the virus adapted to a new host. Since 1977, four human deaths from EBLVs have been reported. None of them had a record of prophylactic rabies immunization. Only fragmentary data exist about the effectiveness of current vaccines in cross-protection against EBLVs. It is clear that EBLV in bats cannot be eliminated using conventional strategies similar to the control programmes based on vaccine baits used for fox rabies in Europe during the 1980s. Due to the protected status of bats in Europe, our knowledge of EBLV prevalence and epidemiology is limited. It is possible that EBLV is under-reported and that the recorded cases of EBLV represent only a small proportion of the actual number of infected bats. For this reason, any interaction between man and bats in Europe must be considered as a possible exposure. Human exposure through biting incidents, especially unprovoked attacks, should be treated immediately with rabies post-exposure treatment and the bat, where possible, retained for laboratory analysis. Preventative measures include educating all bat handlers of the risks posed by rabies-infected animals and advising them to be immunized. This review provides a brief history of EBLVs, their distribution in host species and the public health risks.