Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection

The outbreak of coronavirus disease 2019 (COVID‐19) and pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has become a major concern globally. As of 14 April 2020, more than 1.9 million COVID‐19 cases have been reported in 185 countries. Some patients with COVID‐19 develop severe clinical manifestations, while others show mild symptoms, suggesting that dysregulation of the host immune response contributes to disease progression and severity. In this review, we have summarized and discussed recent immunological studies focusing on the response of the host immune system and the immunopathology of SARS‐CoV‐2 infection as well as immunotherapeutic strategies for COVID‐19. Immune evasion by SARS‐CoV‐2, functional exhaustion of lymphocytes, and cytokine storm have been discussed as part of immunopathology mechanisms in SARS‐CoV‐2 infection. Some potential immunotherapeutic strategies to control the progression of COVID‐19, such as passive antibody therapy and use of interferon αβ and IL‐6 receptor (IL‐6R) inhibitor, have also been discussed. This may help us to understand the immune status of patients with COVID‐19, particularly those with severe clinical presentation, and form a basis for further immunotherapeutic investigations.     

Chimeric antigen receptor (CAR) immunotherapy: basic principles,current advances,and future prospects in neuro-oncology

With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR T cell therapy potential in the field of neuro-oncology. Glioblastoma (GBM) is identified as one of the most challenging solid tumors with a permissive immunological milieu and dismal prognosis. Standard multimodal treatment using maximal safe resection, radiochemotherapy, and maintenance chemotherapy extends the overall survival beyond a year. Recurrence is, however, inevitable. GBM holds several unique features including its vast intratumoral heterogeneity, immunosuppressive environment, and a partially permissive anatomic blood–brain barrier, which offers a unique opportunity to investigate new treatment approaches. Tremendous efforts have been made in recent years to investigate novel CAR targets and target combinations with standard modalities for solid tumors and GBM to improve treatment efficacy. In this review, we outline the history of CAR immunotherapy development, relevant CAR target antigens validated with CAR T cells as well as preclinical approaches in combination with adjunct approaches via checkpoint inhibition, bispecific antibodies, and second-line systemic therapies that enhance anticancer efficacy of the CAR-based cancer immunotherapy.

     

Community acceptance and willingness-to-pay for a hypothetical Zika vaccine: A cross-sectional study in Indonesia

Background

Understanding people’s perceptions of the economic benefits of a potential Zika vaccine (ZV) is critical to accelerating its introduction into either public sector programs or private market. The aim of this study was to assess the acceptance and willingness-to-pay (WTP) for a hypothetical ZV and the associated explanatory variables in Indonesia.

Co-Circulation of Chikungunya and Multiple DENV Serotypes and Genotypes,Western Indonesia 2015–2016

Dengue is a mosquito-borne disease of public health concern affecting tropical and subtropical countries, including Indonesia. Although studies on dengue epidemiology have been undertaken in Indonesia, data are lacking in many areas of the country. The aim of this study was to determine dengue virus (DENV) and chikungunya virus (CHIKV) molecular epidemiology in western regions of the Indonesian archipelago. A one-year prospective study was conducted in Aceh and Jambi in 2015 and 2016, respectively, where patients with dengue-like illness were enrolled. Of 205 patients recruited, 29 and 27 were confirmed with dengue in Aceh and Jambi, respectively, and three from Jambi were confirmed with chikungunya. DENV-1 was the predominant serotype identified in Aceh while DENV-2 was predominant in Jambi. All DENV-1 and DENV-2 from both regions were classified as Genotype I and Cosmopolitan genotype, respectively, and all DENV-3 viruses from Jambi were Genotype I. Some viruses, in particular DENV-1, displayed a distinct lineage distribution, where two DENV-1 lineages from Aceh were more closely related to viruses from China instead of Jambi highlighting the role of travel and flight patterns on DENV transmission in the region. DENV-2 from both Aceh and Jambi and DENV-3 from Jambi were all closely related to Indonesian local strains. All three CHIKV belonged to Asian genotype and clustered closely with Indonesian CHIKV strains including those previously circulating in Jambi in 2015, confirming continuous and sustainable transmission of CHIKV in the region. The study results emphasize the importance of continuous epidemiological surveillance of arboviruses in Indonesia and simultaneous testing for CHIKV among dengue-suspected patients.     

Hyperendemic Dengue and Possible Zika Circulation in the Westernmost Region of the Indonesian Archipelago

The transmission of dengue and other medically important mosquito-borne viruses in the westernmost region of Indonesia is not well described. We assessed dengue and Zika virus seroprevalence in Aceh province, the westernmost area of the Indonesian archipelago. Serum samples collected from 199 randomly sampled healthy residents of Aceh Jaya in 2017 were analyzed for neutralizing antibodies by plaque reduction neutralization test (PRNT). Almost all study participants (198/199; 99.5%) presented with multitypic profiles of neutralizing antibodies to two or more DENV serotypes, indicating transmission of multiple DENV in the region prior to 2017. All residents were exposed to one or more DENV serotypes by the age of 30 years. The highest geometric mean titers were measured for DENV-4, followed by DENV-1, DENV-2 and DENV-3. Among a subset of 116 sera, 27 neutralized ZIKV with a high stringency (20 with PRNT₉₀ > 10 and 7 with PRNT₉₀ > 40). This study showed that DENV is hyperendemic in the westernmost region of the Indonesian archipelago and suggested that ZIKV may have circulated prior to 2017.     

Dengue viruses circulating in Indonesia: A systematic review and phylogenetic analysis of data from five decades

Although epidemiological and molecular epidemiological (serotype, genotype, and lineage information) data are available for several major cities in Indonesia, there is yet to be a comprehensive national study of dengue in Indonesia over time. This study was conducted to provide a comprehensive epidemiology of circulating dengue viruses (DENV) in Indonesia between 1973 and 2016. This was conducted through a systematic review of the literature and phylogenetic analysis of available DENV sequences. Available data from National Disease Surveillance System have indicated an increasing trend of dengue incidence in Indonesia over the past 50 years. Incidence rates appear to be cyclic, peaking approximately every 6 to 8 years. In contrast, the case fatality rate has decreased approximately by half with each decade since 1980. Over this 50‐year time span, serotype shifts, genotype displacement within DENV‐1 and DENV‐2, and introduction of DENV‐1 and DENV‐3 genotype from other countries occurred. These events were associated with increased incidence of dengue cases. Our study also provides a valuable national snapshot of DENV genetic diversity in Indonesia that may contribute to development of more effective dengue vaccine compositions for the region.