COVID-19 Pandemic: lessons learnt and the way forward

Although the scientific community had been predicting and preparing for a pandemic for the last 10 years, many policy makers did not envision that a virus could cause such devastation to human life, economies and to the social structure. COVID-19 has taught us many bitter lessons and while moving forward it is important to understand that this current pandemic is yet to end. However, COVID-19 is unlikely to be the last pandemic that we face, Due to certain human activities such as urbanization, deforestation, increased human and animal interactions and climate change, we will see more pandemics emerging in the coming years. Preparedness and anticipation of such an event is the only way forward

HLA Class I and Class II Associations in Dengue Viral Infections in a Sri Lankan Population

BACKGROUND: HLA class I and class II alleles have been shown to be associated with the development of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) in different populations. However, the majority of studies have been based on limited numbers of patients. In this study we aimed to investigate the HLA-class I and class II alleles that are positively and negatively associated with the development of DSS in a cohort of patients with DHF and also the alleles associated with development of DHF during primary dengue infections in a Sri Lankan population. METHODOLOGY/PRINCIPAL FINDINGS: The allele frequencies of HLA class I and class II alleles were compared in 110 patients with DHF and 119 individuals from the population who had never reported a symptomatic dengue infection at the time of recruitment. We found that HLA-A*31 (corrected P = 0.01) and DRB1*08 (corrected P = 0.009) were associated with susceptibility to DSS when infected with the dengue virus, during secondary dengue infection. The frequency of DRB1*08 allele was 28.7 times higher than in the normal population in patients with DSS. HLA-A*31 allele was increased 16.6 fold in DHF who developed shock when compared to those who did not develop shock. A*24 (corrected P = 0.03) and DRB1*12 (corrected P = 0.041) were strongly associated with the development of DHF during primary dengue infection. CONCLUSIONS/SIGNIFICANCE: These data suggest that certain HLA alleles confer susceptibility/protection to severe dengue infections. As T cell epitope recognition depend on the HLA type of an individual, it would be now important to investigate how epitope specific T cells associate with primary and secondary dengue infections and in severe dengue infections

Viral Load, Clinical Disease Severity and Cellular Immune Responses in Primary Varicella Zoster Virus Infection in Sri Lanka

BACKGROUND: In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied. METHODOLOGY: We used IFNgamma ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection. PRINCIPAL FINDINGS: Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p<0.001) and were significantly higher in those over 25 years of age (P<0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNgamma ELISpot responses of patients (P<0.001, r = -0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation. CONCLUSIONS: Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses

Investigation of varicella zoster virus glycoprotein-specific T cell responses

T cells are believed to be important in the control of varicella zoster virus (VZV) replication but little is known of T cell epitopes and the relationships between T cell responses, viral load and clinical disease during primary infection.I initially set to investigate the immune responses to two of the main VZV glycoproteins (gE and gI) using ex vivo and cultured IFNγ ELISpot assays. I identified several novel CD4+ T cell epitopes within gE and gI and characterized the phenotype of gE DRB1*1501 tetramer specific responses in healthy immune donors. I then set out to investigate the function and phenotype of VZV specific T cells in primary infection and their relationship to viral loads and clinical disease severity by using glycoprotein E/DRB1*1501 specific MHC class II tetramers, ex vivo IFNγ ELISpot assays and quantitative real time PCR assays. I compared the frequency and phenotype of specific T cells with virological and clinical outcomes in 32 adult individuals with primary VZV infection.In healthy immune donors, the gE specific T cells showed a early intermediate stage of differentiation with evidence of recent activation. Patients with acute primary infection had higher VZV/DRB1*1501 tetramer specific T cell responses and expressed markers of activation and effector differentiation. Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p&lt;0.001). A significant inverse correlation was seen between the viral loads and the ex vivo IFNγ ELISpot responses of the patients (p&lt;0.05, r=-0.64).These data would be compatible with a role for gE and gl-specific T cells in the control of viral replication during both primary infection and re-activation.</p

Investigation of varicella zoster virus glycoprotein-specific T cell responses

T cells are believed to be important in the control of varicella zoster virus (VZV) replication but little is known of T cell epitopes and the relationships between T cell responses, viral load and clinical disease during primary infection. I initially set to investigate the immune responses to two of the main VZV glycoproteins (gE and gI) using ex vivo and cultured IFNγ ELISpot assays. I identified several novel CD4+ T cell epitopes within gE and gI and characterized the phenotype of gE DRB1*1501 tetramer specific responses in healthy immune donors. I then set out to investigate the function and phenotype of VZV specific T cells in primary infection and their relationship to viral loads and clinical disease severity by using glycoprotein E/DRB1*1501 specific MHC class II tetramers, ex vivo IFNγ ELISpot assays and quantitative real time PCR assays. I compared the frequency and phenotype of specific T cells with virological and clinical outcomes in 32 adult individuals with primary VZV infection. In healthy immune donors, the gE specific T cells showed a early intermediate stage of differentiation with evidence of recent activation. Patients with acute primary infection had higher VZV/DRB1*1501 tetramer specific T cell responses and expressed markers of activation and effector differentiation. Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p<0.001). A significant inverse correlation was seen between the viral loads and the ex vivo IFNγ ELISpot responses of the patients (p<0.05, r=-0.64). These data would be compatible with a role for gE and gl-specific T cells in the control of viral replication during both primary infection and re-activation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Rapid effector function of varicella-zoster virus glycoprotein I-specific CD4+ T cells many decades after primary infection

Glycoprotein I (gI) of varicella-zoster virus (VZV) contributes to viral virulence and is therefore a potentially important target for T cell control of viral replication. Persisting effector function of gI-specific T cells after primary infection has not been previously examined. We have shown that, many decades after infection, relatively high frequencies gI-specific interferon- gamma responses are detectable ex vivo and are dominated by CD4(+) T cells. We characterized the optimal peptide of the strongest response in our cohort showing restriction through DRB4*01. These findings are consistent with gI-specific CD4(+) T cell involvement in the control of VZV replication

Pathogenesis of Dengue viral infections

Dengue viral infections are one of the most important mosquito borne viral infections in the world. There are four dengue virus serotypes (DEN1-4) which are closely related. Initial infection with a particular serotype is known as primary infection, which is usually asymptomatic or results in mild disease manifestations. Although cross reactive T cells and cross reactive antibodies have been shown to contribute to disease pathogenesis, these mechanisms alone do not explain the immunopathological mechanisms leading to severe disease. However, studies have suggested that immunopathological, host genetic and viral factors all contribute to the occurrence of severe disease. Therefore, it is important to further investigate the quality of dengue specific immune responses in patients with acute severe and asymptomatic dengue infection, to determine the immune correlates of severe clinical disease and protection.DOI: http://dx.doi.org/10.4038/sljid.v1i1.2987 Sri Lankan Journal of Infectious Diseases Vol.1(1) 2011: 2-8</p