RESUMO
Till now, AIDS, caused by the human immunodeficiency virus (HIV) is still a severe health problem worldwide. It weakens the immune system by targeting the T-helper cells. Specifically, the severity of the pandemic HIV-1 makes the emergence of an enduring effective vaccine against HIV-1. Therefore, we have applied a series of immunoinformatics approaches to the four conserved domains of HIV-1 integrase (IN) proteins to design an effective multi-epitope based subunit vaccine which might induce a competent immunity against HIV-1. Therefore, we have selected three peptide fragments that contained all overlapping epitopes (35 CD4+, 8 CD8+ T-cell epitopes, and 3â¯B-cell epitopes) where the epitopes had a high conservancy score. The cumulative population coverage for combined CD8+ and CD4+ T-cell epitopes and their respective HLA-alleles were found as 98.03% in the world which is also followed by East Asia (96.24%), South Asia (96.31%), North Africa (96.14%), North America (98.99%), and Europe (98.80%). The proposed vaccine composed by an adjuvant (ß-defensin) at the N-terminal site of the vaccine constructs and three peptide fragments where the adjuvant was fused by EAAAK linker and the peptide fragments were fused by GPGPG linker. The designed final vaccine construct (length: 159 amino acid) was found to be antigenic and non-allergic, which indicates its safety. The vaccine construct was found as good antigenic, stable, higher thermostable, and hydrophilic in nature. The codon adaptation and in silico cloning ensured the high expression rate of the vaccine constructs in E. coli K12 with CAI value of 1.0. Finally, the binding affinity of the vaccine constructs with the immune receptor TLR3 was confirmed by the lowest energy score of -1026.8 evaluated by molecular docking. However, the proposed in silico vaccine construct needs experimental validation for assuring the safety and immunogenicity profile which will ensure an active immunity against HIV-1.
Assuntos
Vacinas contra a AIDS/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Infecções por HIV/imunologia , Integrase de HIV/imunologia , HIV-1/imunologia , Vacinas contra a AIDS/genética , Sequência de Aminoácidos , Ásia , Biologia Computacional , Epitopos de Linfócito B/química , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/química , Epitopos de Linfócito T/genética , Europa (Continente) , Infecções por HIV/genética , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Integrase de HIV/química , Integrase de HIV/genética , HIV-1/química , HIV-1/genética , Humanos , Simulação de Acoplamento Molecular , Domínios Proteicos , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
A comparative study was done to compare risks and benefits of normal vaginal and caesarean section delivery. One hundred women between 36 to 40 weeks gestation were enrolled and face to face interviews and clinical assessments were conducted both in antenatal and postnatal period. Though 98% preferred vaginal birth only 45% eventually had so. Both immediate and late complications were considerably more in caesarian section than in normal vaginal delivery. Mean duration of sickness and mean days required for returning to normal activities were also higher in case of caesarian section. The average cost for Caesarian was $70 while for normal vaginal delivery it was $28. Caesarean delivery has some associated risks and complications. It is expensive than normal vaginal delivery. It will help practitioners to reduce the rate of primary caesarean delivery and the pregnant mothers should be informed about risks and benefits of various birth options.