Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women-to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.
COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 μg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.
The Enzyme-Linked Immunosorbent Assay is a versatile technique, which can be used for several applications. It has enormously contributed to the study of infectious diseases. This review highlights how this methodology supported the science conducted in COVID-19 pandemics, allowing scientists to better understand the immune response against SARS-CoV-2. ELISA can be modified to assess the functionality of antibodies, as avidity and neutralization, respectively by the standardization of avidity-ELISA and surrogate-neutralization methods. Cellular immunity can also be studied using this assay. Products secreted by cells, like proteins and cytokines, can be studied by ELISA or its derivative Enzyme-linked immunospot (ELISpot) assay. ELISA and ELISA-based methods aided the area of immunology against infectious diseases and is still relevant, for example, as a promising approach to study the differences between natural and vaccine-induced immune responses against SARS-CoV-2.
Vaccines are the most effective tool to control infectious diseases, which provoke significant morbidity and mortality rates. Most vaccines are administered through the parenteral route and can elicit a robust systemic humoral response, but they induce a weak T-cell-mediated immunity and are poor inducers of mucosal protection. Considering that most pathogens enter the body through mucosal surfaces, a vaccine that elicits protection in the first site of contact between the host and the pathogen is promising. However, despite the advantages of mucosal vaccines as good options to confer protection on the mucosal surface, only a few mucosal vaccines are currently approved. In this review, we discuss the impact of vaccine administration in different mucosal surfaces; how appropriate adjuvants enhance the induction of protective mucosal immunity and other factors that can influence the mucosal immune response to vaccines.
Background: Neisseria meningitidis is the main cause of bacterial meningitis in Brazil, where the main serogroups isolated are B and C; however, the serogroup W has recently emerged. LPS and type IV pili are important virulence factors that increase meningococci pathogenicity. Methods: The characterization of Lipopolysaccharide (LPS) and type IV pili in 19 meningococci strains of serogroup B, 21 of serogroup C, 45 of serogroup W and 28 of serogroup Y, isolated in Brazil between 2011 and 2017, was conducted using the Enzyme-linked Immunosorbent Assay (Dot- ELISA) technique and monoclonal antibodies. Results: We would like to emphasize the importance of characterizing relevant antigens, such as pili and LPS, the use of monoclonal antibodies to support it, and how such studies improve vaccine development and monitoring. Most of the strains studied presented L3,7,9 LPS and type IV pili; both antigens are associated with the capacity to cause invasive disease. Conclusion: Due to the impact of meningococcal disease, it is important to maintain and improve vaccine studies. Epitopes characterization provides data about the virulence of circulating strains. The use of monoclonal antibodies and serological techniques are relevant and support vaccine development.
The emergence and re-emergence of pathogens is a public-health concern, which has become more evident after the coronavirus disease 2019 (COVID-19) pandemic and the monkeypox outbreaks in early 2022. Given that vaccines are the more effective and affordable tools to control infectious diseases, the authors reviewed two heterologous effects of vaccines: the trained immunity and the cross-reactivity. Trained immunity, provided by attenuated vaccines, was exemplified in this article by the decreased the burden of COVID-19 in populations with high Bacille Calmette-Guerin (BCG) coverage. Cross-reactive responses were exemplified here by the studies which suggested that vaccinia could help controlling the monkeypox outbreak, because of common epitopes shared by orthopoxviruses. Although modern vaccination is likely to use subunit vaccines, the authors discussed how adjuvants might be the key to induce trained immunity and improve cross-reactive responses, ensuring that heterologous effects would improve the vaccine’s response.
Immunization against Neisseria meningitidis is important for public health. Vaccines composed of cross-reactivity antigens avoid strain-specific responses, ensuring more comprehensive protection.The cross-reactivity between three strains from the last outbreak of N. meningitidis in Brazil was assessed in our studies, using enzyme-linked immunosorbent assay (ELISA) and immunoblotting assays.Both assays verifed a similar humoral response between the strains evaluated. Patterns of antigen recognition differed with each dose evaluated.We observed that immunization with N. meningitidis B outer membrane vesicles (OMVs) led to the production of antibodies that recognized antigens of heterologous strains, indicating possible protection against these evaluated strains.
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