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All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays.

ABH antigens are histo-antigens, but were first described on the surface of human erythrocytes. They are found in those cells only in great apes and humans, while in more primitive animals they are found in tissues and body fluids. ABH antigens are mainly distributed in tissues that are in contact with the external environment and may serve as ligands for pathogens in tissues or block their connection. Description of the distribution of these molecules in non-human primate tissues is restricted to a few tissues and species. This paper describes the expression of human A, B and H type antigens in different organs from four species of New World Primates, obtained from the Centro Nacional de Primatas, as well as comparing that expression with what has been described for humans. In this study, although the tissue description of the antigens is similar to the genetic model for humans, some differences in expression between some organs from those species and those of humans were found. The differences occurred mainly in endodermal organs that have secretory functions and are probably under the control of the human-type FUT-2 enzyme. In the mesodermal-origin organs there was a reduction or absence of A and B antigen marking, particularly in the H precursor substance, indicating that those organs are under the control of the human-type FUT-1 enzyme. These findings have demonstrated that there is similar ABH antigen reactivity in tissue distribution between the species, although there are some species-specific cases.

Measuring binding properties of binders (e.g., antibodies) is essential for developing useful experimental reagents, diagnostics, and pharmaceuticals. Display technologies can evaluate a large number of binders in a high-throughput manner, but the immobilization effect and the avidity effect prohibit the precise evaluation of binding properties. In this paper, we propose a novel methodology, peptide barcoding, to quantitatively measure the binding properties of multiple binders without immobilization. In the experimental scheme, unique peptide barcodes are fused with each binder, and they represent genotype information. These peptide barcodes are designed to have high detectability for mass spectrometry, leading to low identification bias and a high identification rate. A mixture of different peptide-barcoded nanobodies is reacted with antigen-coated magnetic beads in one pot. Peptide barcodes of functional nanobodies are cleaved on beads by a specific protease, and identified by selected reaction monitoring using triple quadrupole mass spectrometry. To demonstrate proof-of-principle for peptide barcoding, we generated peptide-barcoded anti-CD4 nanobody and anti-GFP nanobody, and determined whether we could simultaneously quantify their binding activities. We showed that peptide barcoding did not affect the properties of the nanobodies, and succeeded in measuring the binding activities of these nanobodies in one shot. The results demonstrate the advantages of peptide barcoding, new types of genotype–phenotype linkages.

Haemonchus contortus is the most pathogenic gastrointestinal helminth of small ruminants. Natural or experimental repeated infections and several native antigens confer a partially protective immune response but vaccination with subunit antigens has been elusive. Promising results have been obtained with a recombinant form of a somatic antigen (rHc23). In this paper we present the results obtained in vaccination trials in lambs using two dosages of rHc23 and standard adjuvants. Six-months old Manchego females lambs were vaccinated with rHc23 (50 or 200 μg/dose) adjuvanted with 1mL aluminum hydroxide on days -42, -28 and -14 or with 200 μg/dose rHc23 and 5 mg Quil A on days -49, -28 and -7. Control lambs were kept receiving only the adjuvants the same days or no treatment. Moreover one group did not receive any treatment or infection. On day 0 vaccinated lambs, untreated animals and those receiving the adjuvant were infected per os with a monospecific single infection of 4000 L3 of H. contortus. Infection was kept for 58 days and follow-up included the determination of serum specific antibody response (ELISA, WB), hematological parameters (eosinophil counts, hematocrit) and fecal egg counts (epg). Absence of hematocrit alterations, reduction of helminth's eggs output and abomasal parasite burden at the end of the experiment were the efficacy criteria of vaccination with the recombinant. Immunization with both adjuvants and antigen dosages elicited strong antibody responses particularly with Quil A. Vaccinated groups showed significant reduction of fecal egg excretion and abomasal helminth burdens. Highest protection of lambs against challenge was achieved with aluminum hydroxide and 200 μg/dose rHc23 with a reduction of over 70% of the abomasal burden and over 80% of fecal egg output. Results suggest that rHc23 could be a valuable recombinant candidate for vaccination against haemonchosis. No clear relationship was found between antibody levels and protection this pointing towards involvement of both humoral and cellular components in the protective response elicited by rHc23.

With the HIV-1 epidemic in southern Africa still rising, a prophylactic vaccine against the region's most prolific subtype (subtype C) would be a significant step forward. In this paper we report on the effect of 2 different adjuvants, AddaVax and AlhydroGel, formulated with HIV-1 subtype C gp140, on the development of binding and neutralising antibody titres in rabbits. AddaVax is a squalene-based oil-in-water nano-emulsion (similar to MF59) which can enhance both cellular and humoral immune responses, whilst AlhydroGel (aluminium hydroxide gel) mainly drives a Th2 response. The gp140 gene tested was derived from the superinfecting virus (SU) from participant CAP256 in the CAPRISA 002 Acute infection cohort. The furin cleavage site of the Env protein was replaced with a flexible linker and an I559P mutation introduced. Lectin affinity purified soluble Env protein was mainly trimeric as judged by molecular weight using BN-PAGE and contained intact broadly neutralising epitopes for the V3-glycan supersite (monoclonal antibodies PGT128 and PGT135), the CD4 binding site (VRC01) and the V2-glycan (PG9) but not for the trimer-specific monoclonal antibodies PG16, PGT145 and CAP256-VRC26_08. When this soluble Env protein was tested in rabbits, AlhydroGel significantly enhanced soluble Env and V1V2 binding antibodies when compared to AddaVax. Finally, AlhydroGel resulted in significantly higher neutralization titres for a subtype C Tier 1A virus (MW965.26) and increased neutralization breadth to Tier 1A and 1B viruses. However, no autologous Tier 2 neutralisation was observed. These data suggest that adjuvant selection is critical for developing a successful vaccine and AlhydroGel should be further investigated. Additional purification of trimeric native-like CAP256 Env and/or priming with DNA or MVA might enhance the induction of neutralizing antibodies and possible Tier 2 HIV-1 neutralisation.

Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011-2012 winter season and finally, during the 2013-2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease. In this paper, we analyzed the evolution, antigenic and genetic drift of Mexican isolates from 2009, at the beginning of the pandemic, to 2014. We found a clear variation of the virus in Mexico from the 2011-2014 season due to different markers and in accordance with previous reports. In this study, we identified 13 novel substitutions with important biological effects, including virulence, T cell epitope presented by MHC and host specificity shift and some others substitutions might have more than one biological function. The systematic monitoring of mutations on whole genome of influenza A pH1N1 (2009) virus circulating at INER in Mexico City might provide valuable information to predict the emergence of new pathogenic influenza virus.

Agent-based simulation is a powerful method for investigating the complex interplay of the processes occurring in a lymph node during an adaptive immune response. We have previously established an agent-based modeling framework for the interactions between T cells and dendritic cells within the paracortex of lymph nodes. This model simulates in three dimensions the "random-walk" T cell motility observed in vivo, so that cells interact in space and time as they process signals and commit to action such as proliferation. On-lattice treatment of cell motility allows large numbers of densely packed cells to be simulated, so that the low frequency of T cells capable of responding to a single antigen can be dealt with realistically. In this paper we build on this model by incorporating new numerical methods to address the crucial processes of T cell ingress and egress, and chemotaxis, within the lymph node. These methods enable simulation of the dramatic expansion and contraction of the T cell population in the lymph node paracortex during an immune response. They also provide a novel probabilistic method to simulate chemotaxis that will be generally useful in simulating other biological processes in which chemotaxis is an important feature.