Therapeutic Advances in Vaccines and Immunotherapy最新文献

While antibodies garner the lion's share of attention in SARS-CoV-2 immunity, cellular immunity (T cells) may be equally, if not more important, in controlling infection. Both CD8⁺ and CD4⁺ T cells are elicited earlier and are associated with milder disease, than antibodies, and T-cell activation appears to be necessary for control of infection. Variants of concern (VOCs) such as Omicron have escaped the neutralizing antibody responses after two mRNA vaccine doses, but T-cell immunity is largely intact. The breadth and patient-specific nature of the latter offers a formidable line of defense that can limit the severity of illness, and are likely to be responsible for most of the protection from natural infection or vaccination against VOCs which have evaded the antibody response. Comprehensive searches for T-cell epitopes, T-cell activation from infection and vaccination of specific patient groups, and elicitation of cellular immunity by various alternative vaccine modalities are here reviewed. Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed. While VOCs have not yet fully escaped T-cell immunity elicited by natural infection and vaccines, some early reports of partial escape suggest that future VOCs may achieve the dreaded result, dislodging a substantial proportion of cellular immunity, enough to cause a grave public health burden. A proactive, rather than reactive, solution which identifies and targets immutable sequences in SARS-CoV-2, not just those which are conserved, may be the only recourse humankind has to disarm these future VOCs before they disarm us.

Background: Historically, there have been many factors that have influenced mumps, measles and rubella (MMR) vaccine uptake, including media bias, social/economic determinants, parental education level, deprivation and concerns over vaccine safety. Readability metrics through online tools are now emerging as a means for healthcare professionals to determine the readability of patient-facing vaccine information. The aim of this study was to examine the readability of patient-facing materials describing MMR vaccination, through employment of nine readability and text parameter metrics, and to compare these with MMR vaccination literature for healthcare professionals and scientific abstracts relating to MMR vaccination.

Materials and methods: The subscription-based online Readable program (readable.com) was used to determine nine readability indices using various readability formulae: Established readability metrics (n = 5) (Flesch-Kinkaid Grade Level, Gunning Fog Index, SMOG Index, Flesch Reading Ease and New Dale-Chall Score), as well as Text parameters (n = 4) (sentence count, word count, number of words per sentence, number of syllables per word) with 47 MMR vaccination texts [patient-facing literature (n = 22); healthcare professional-focused literature (n = 8); scientific abstracts (n = 17)].

Results: Patient-facing vaccination literature had a Flesch Reading Ease score of 58.4 and a Flesch-Kincaid Grade Level of 8.1, in comparison with poorer readability scores for healthcare professional literature of 30.7 and 12.6, respectively. MMR scientific abstracts had the poorest readability (24.0 and 14.8, respectively). Sentence structure was also considered, where better readability metrics were correlated with significantly lower number of words per sentence and less syllables per word.

Conclusion: Use of these readability tools enables the author to ensure their research is more readable to the lay audience. Patient co-production initiatives would help to ensure that not only can the target audience read the literature, but that they understand the content. Increased patient-centric focus groups would give better insights into reasons for MMR-associated vaccine hesitation and vaccine refusal.

Measles-rubella (MR) vaccine-associated encephalopathy is rare and coexistence with optic neuritis (ON) has never been reported. Only two patients (one child and one adult) had 'MR Vaccine-associated myelin-oligodendrocyte-glycoprotein antibody (MOGAb) positive encephalopathy'. Myelin oligodendrocyte glycoprotein (MOG), a surface myelin protein, is the target of the immune system in this disease. We describe a critical unique case of 'post-MR Vaccine, MOG-antibody positive Acute Disseminated Encephalo-Myelitis (ADEM) with optic neuritis', who recovered with immunotherapy.

Background: COVID-19 infections among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-vaccinated individuals are of clinical concern, especially in those requiring hospitalization. Such real-world data on ChAdOx1 nCoV-19- and BBV152-vaccinated individuals are scarce. Hence, there is an urgent need to understand their clinical profile and outcomes.

Methods: A 1:1 pair-matched study was performed among vaccinated and unvaccinated COVID-19 patients admitted between March 2021 and June 2021 at a tertiary care centre in New Delhi, India. The vaccinated group (received at least one dose of ChAdOx1 nCoV-19 or BBV152) was prospectively followed till discharge or death and matched [for age (±10 years), sex, baseline disease severity and comorbidities] with a retrospective group of unvaccinated patients admitted during the study period. Paired analysis was done to look for clinical outcomes between the two groups.

Results: The study included a total of 210 patients, with 105 in each of the vaccinated and unvaccinated groups. In the vaccinated group, 47 (44.8%) and 58 (55.2%) patients had received ChAdOx1 nCoV-19 and BBV152, respectively. However, 73 patients had received one dose and 32 had received two doses of the vaccine. Disease severity was mild in 36.2%, moderate in 31.4% and severe in 32.4%. Two mortalities were reported out of 19 fully vaccinated individuals. All-cause mortality in the vaccinated group was 8.6% (9/105), which was significantly lower than the matched unvaccinated group mortality of 21.9% (23/105), p = 0.007. Vaccination increased the chances of survival (OR = 3.8, 95% CI: 1.42-10.18) compared to the unvaccinated group.

Conclusion: In the second wave of the pandemic predominated by delta variant of SARS CoV-2, vaccination reduced all-cause mortality among hospitalized patients, although the results are only preliminary.

Approximately 2.3 million people are suffering from human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection worldwide. Faster disease progression and increased mortality rates during the HIV/HCV co-infection have become global health concerns. Effective therapeutics against co-infection and complete infection eradication has become a mandatory requirement. The study of small non-coding RNAs in cellular processes and viral infection has so far been beneficial in various terms. Currently, microRNAs are an influential candidate for disease diagnosis and treatment. Dysregulation in miRNA expression can lead to unfavorable outcomes; hence, this exact inevitable nature has made various studies a focal point. A considerable improvement in comprehending HIV and HCV mono-infection pathogenesis is seen using miRNAs. The prominent reason behind HIV/HCV co-infection is seen to be their standard route of transmission, while some pieces of evidence also suspect viral interplay between having a role in increased viral infection. This review highlights the involvement of microRNAs in HIV/HCV co-infection, along with their contribution in HIV mono- and HCV mono-infection. We also discuss miRNAs that carry the potentiality of becoming a biomarker for viral infection and early disease progression.

Coronavirus disease 2019 (COVID-19) has made a global impact on the daily lives of humanity, devastating health systems, and cataclysmically affecting the world's economy. Currently, the Standard Public Health Protective practices consist of but are not limited to wearing masks, social distancing, isolating sick and exposed people, and contact tracing. Scientists around the globe undertook swift scientific efforts to develop safe and effective therapeutics and vaccines to combat COVID-19. Presently, as of mid-March 2022, 57.05% of the world population have been fully vaccinated, and 65.3% of the United States of America's (USA) total population have been fully vaccinated while 76.7% have received at least one dose of the vaccine. This article explores the various vaccines created through modern science and technology, including their safety, efficacy, and mechanism of action. Although the vaccines produced are up to 95.0% efficacious, their efficacy wanes over time, underscoring the need for booster doses. Also, vaccination has not been able to prevent "breakthrough" infections. The limitations of the SARS-CoV-2 vaccines indicate that further measures are required to ensure a firm control of the COVID-19 pandemic. Therefore, the Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the use of certain therapeutic agents because they have shown remarkable clinical outcomes. Several therapeutic agents for the treatment of mild-to-moderate COVID-19 include Gilead's remdesivir, Regeneron's casirivimab and imdevimab combination, Eli Lilly's baricitinib and remdesivir combination, Pfizer's co-packaged nirmatrelvir tablets and ritonavir tablets, and Merck's molnupiravir capsules. Hence concerted efforts in early and accurate diagnosis, education on the COVID-19 virulence, transmission and preventive measures, global vaccination, and therapeutic agents could bring this COVID-19 pandemic under control across the globe.

Herpes zoster (HZ) is a neurocutaneous disease that causes significant morbidity worldwide. The disease is caused by the reactivation of the varicella-zoster virus (VZV), which leads to the development of a painful, vesicular rash and can cause complications such as post-herpetic neuralgia and vision loss. Globally, the incidence of HZ is increasing, and it incurs billions in cost annually to the healthcare system and to society through loss of productivity. With the advent of effective vaccines such as the live attenuated vaccine, Zostavax^®, in 2006, and more recently the adjuvant recombinant subunit vaccine, Shingrix^®, in 2017, HZ has become a preventable disease. However, access to the vaccines remains mostly limited to countries with developed economies, such as the United States and Canada. Even among countries with developed economies that license the vaccine, few have implemented HZ vaccination into their national immunization schedules due to cost-effectiveness considerations. In this review, we discuss the currently available HZ vaccines, landscape of HZ vaccine guidelines, and economic burden of disease in countries with developed and developing economies, as well as barriers and considerations in HZ vaccine access on a global scale.