Developing an efficacious vaccine for SARS-CoV-2 infection is critical to stemming COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in designing an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers and 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC I and II alleles, respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. With our In silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We, therefore, propose that potential vaccine designs consider this approach.

A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/cei.12861This article is protected by copyright. All rights reserved. 2 ABSTRACTTuberculosis (TB) causes significant morbidity and mortality on a global scale. The African region has 24% of the world TB cases. TB overlaps with other infectious diseases such as malaria and HIV which are also highly prevalent in the African region. TB is a leading cause of death among HIVpositive patients and co-infection with HIV and TB has been described as a syndemic. In view of the overlapping epidemiology of these diseases, it is important to understand the dynamics of the immune response to TB in the context of co-infection. We investigated the cytokine response to purified protein derivative (PPD) in peripheral blood mononuclear cells from TB patients coinfected with HIV or malaria and compared it to that of malaria-and HIV-free TB patients. A total of 231 subjects were recruited for this study and classified into 6 groups; Untreated TB positive, TB positive subjects on TB drugs, TB and HIV positive, TB and malaria positive, latent TB, and apparently healthy control subjects. Our results demonstrate maintenance of IFN-γ production in HIV and malaria co-infected TB patients in spite of lower CD4 counts in the HIV-infected cohort. Malaria co-infection caused an increase in the production of the Th2-associated cytokine IL-4 and the anti-inflammatory cytokine IL-10 in PPD-stimulated cultures. These results suggest that malaria co-infection diverts immunity response against M. tuberculosis towards a Th-2/antiinflammatory response which might have important consequences for disease progression. Keywords: tuberculosis, HIV, malaria, co-infection, cytokines Page 32 of 52 Clinical Experimental ImmunologyThis article is protected by copyright. All rights reserved.3 Introduction Tuberculosis (TB) is an infectious disease that causes significant morbidity and mortality on a global scale [1]. Pulmonary tuberculosis caused by infection with Mycobacterium tuberculosis is the leading cause of death due to a bacterial pathogen and is responsible for 1.4 million deaths annually [2]. In 2011, there were an estimated 8.7 million new cases of TB and 1.4 million people died from TB, including almost one million deaths among HIV-negative individuals and 430,000 among people who were HIV positive [3]. TB is second only to HIV/AIDS as the biggest killer worldwide due to a single infectious agent [4]. Host immune response...

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

Background Nigeria contributes significantly to the global burden of HIV, Hepatitis B and C infections, either singly or in combinations, despite progress in HIV care regionally and globally. Although some limited data on mono infection of HIV, Hepatitis B and C virus infections do exists, that of dual and triplex infections, including seroconversion and mother-to-child transmission (MTCT) rates necessary for planning to address the scourge of infections in pregnancy are not available. Objectives To determine the seroprevalence, rate of new infections, MTCT of dual and triple infections of HIV, Hepatitis B and C viruses and associated factors, among pregnant women in Nigeria. Method A multicenter prospective cohort study will be conducted in six tertiary health facilities randomly selected from the six geopolitical zones of Nigeria. All eligible pregnant women are to be tested at enrollment after informed consent for HIV, Hepatitis B and C virus infections. While those positive for at least two of the infections in any combination will be enrolled into the study and followed up to 6 weeks post-delivery, those negative for the three infections or positive for only one of the infections at enrolment will be retested at delivery using a rapid diagnostic test. On enrolment into the study relevant information, will be obtained, and laboratory test of CD4 count, liver function test and full blood counts, and prenatal ultrasonography will also be obtained/performed. Management of mother-newborns pairs will be according to appropriate national guidelines. All exposed newborns will be tested for HIV, HBV or HCV infection at birth and 6 weeks using PCR technique. The study data will be documented on the study case record forms. Data will be managed with SPSS for windows version 23. Ethical approval was obtained from National Health Research Ethics Committee (NHREC) (NHREC/01/01/2007–23/01/2020). Conclusion Pregnant women with multiple of HIV, HBV and HCV infections are at increased risk of hepatotoxicity, maternal and perinatal morbidity and mortality. Additionally, infected pregnant women transmit the virus to their unborn baby even when asymptomatic. Children born with any of the infection have significantly poorer quality of life and lower five-year survival rate. Unfortunately, the seroconversion and MTCT rates of dual or triplex infections among pregnant women in Nigeria have not been studied making planning for prevention and subsequent elimination of the viruses difficult. The study is expected to fill this knowledge gaps. Nigeria joining the rest of the world to eliminate the triple infection among children rest on the availability of adequate and reliable data generated from appropriately designed, and powered study using representative population sample. The establishment of the three-in-one study of prevalence, rate of new infection, rate and risk factor for MTCT of dual and triple infection of HIV, Hepatitis B and C viruses among pregnant women in Nigeria is urgently needed for policy development and planning for the improvement of the quality of life of mothers and the elimination of childhood triplex infection.

Developing an efficacious vaccine to SARS-CoV-2 infection is critical to stem COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in the design of an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers along with 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC-I and II alleles respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. The vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, with triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We therefore propose that potential vaccine designs consider this approach.