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Lobaina, Y.

Publications and source records attributed to Lobaina, Y..

4 recordsLinked to original sources

Synthetic adjuvants to potentiate the immune response against rAg85B by nasal route.

Respiratory infections remain a relevant global health concern nowadays. The rapid dissemination and high mutational ratio of some pathogens, amid human demographic drivers, increases their pandemic potential. On the other hand, some bacterial infections have re-emerged with new resistant variants, supporting the need of updated or more potent vaccines. The development of nasal vaccines, with the capacity to efficiently induce immune response at the respiratory tract and systemic compartments, constitutes an appealing strategy to tackle respiratory infections, including tuberculosis. In this work, two synthetic compounds, the ODN-39M and the peptide LALF32-51, are evaluated as nasal vaccine adjuvants for the Ag85B antigen from Mycobacterium tuberculosis. The capacity of such adjuvants to enhance the immune response at systemic and mucosal compartments following intranasal immunization was assessed in Balb/C mice. The ODN-39M was able to potentiate the immune response, showing preferentially a Th1 pattern. The vaccine preparation containing this CpG adjuvant plus Ag85B induces potent cell-mediated and high IgA specific antibody response in lungs, along with systemic immunity. A preliminary study of the interaction between the ODN-39M with the NALT immune cells shows the early recruitment of lymphoid cells, and the increase of CD69 activation marker, mainly in B and dendritic cells. Although further studies should be done to reach a deeper understanding of NALT functioning, including the development of local innate response, the current data enrich the scarce reports focused on this compartment and support the use of the ODN-39M as a potent and potentially safe adjuvant option for future nasal vaccines.

immunology↗

Immunological evaluation in African Green Monkeys of two nasal vaccine candidates to induce a broad immunity against coronaviruses

The COVID-19 pandemic has had a profound impact on the world. While the disease is currently under control, the emergence of new coronavirus variants with pandemic potential underscores the need for more universal coronavirus vaccines. This study evaluates the immunogenicity in non-human primates of two broad-spectrum nasal vaccine candidates called PanCoV. The vaccine preparations are based on highly conserved regions of SARS-CoV-2, specifically the nucleocapsid (N) and the S2 subunit from Spike protein, which include several relevant T-cell epitopes and have the potential to form virus-like particles. PanCoV1 candidate contains the N protein, while the PanCoV2 comprises a chimeric protein containing the C-terminal domain of N protein fused to a fragment of S2 subunit. Both vaccine candidates also include the receptor-binding domain (RBD) from Spike protein and the ODN-39M as CpG adjuvant. The results demonstrate that both nasal vaccine candidates can boost the anti-RBD immune response and induce anti-N immunity, this systemic response shows cross-reactivity with SARS-CoV, MERS-CoV, and H-CoV antigens. In addition, a neutralizing response against SARS-CoV-2 that persisted for almost three months after the last dose was induced. A mucosal-specific and cross-reactive IgA response was also observed, mainly in monkeys vaccinated with PanCoV2. Furthermore, the specific IFN{gamma}-secreting response observed in the vaccinated groups peripheral blood mononuclear cells highlights the ability of these candidates to stimulate cellular immunity with a Th1 bias. PanCoV vaccines emerge as promising candidates for use as a booster alternative, with the potential to amplify and broaden the scope of the immune response against coronaviruses.

immunology↗

A nasal vaccine candidate, based on S2 and N proteins from SARS-CoV-2, generates a broad antibody response systemic and at lower respiratory tract.

Since the beginning of the COVID-19 pandemic various groups around the world have intensively worked in the development of vaccine candidates against SARS-CoV-2. Several vaccines have been approved in the past years, the majority are based on the Spike or RBD proteins and employs parenteral administration routes. Considering the recent history of Coronavirus zoonotic events, causing serious human health problems, the generation of vaccines with a broad scope of protection and the potential to cut / reduce the transmission remains in the spotlight. The current global pandemic preparedness initiatives have promoted also the preclinical evaluation of a new group of Coronavirus vaccines. In the present work a nasal vaccine candidate based on two highly conserved Sarbecovirus proteins, S2 and nucleocapsid (N), is evaluated in two different mice strains. The vaccine preparation, containing a CpG ODN as adjuvant, was able to generate high antibody titers against both antigens, in sera and bronchoalveolar lavages. This antibody response results cross-reactive to S2 from SARS-CoV-1 and MERS-CoV, and to N from SARS-CoV-1. However, a very low neutralizing capacity was found in the sera of the immunized mice when a pseudoviral system assay was used. On the other hand, the vaccine preparation induces, at systemic compartment, IFN {gamma} secretion, and a marked IgG2a response, specific against both proteins; a profile consistent with the development of a Th1 pattern. Although further evaluations should be done, including protection assays, the demonstrated cross-reactivity level and mucosal response constitutes promising features of this vaccine candidate.

immunology↗

The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

Despite the rapid development of vaccines and their reported efficacy for controlling the COVID-19 waves, two key challenges remain: the scope of the immunity against upcoming variants and zoonosis events, and the induction of mucosal immunity able to clear the virus in the upper respiratory tract for halting the transmission. The present study is aiming at assessing a potential component for a new generation of vaccines so as to overcome such limitations. The recombinant nucleocapsid (N) protein from SARS-CoV-2 Delta variant was combined with a phosphodiester backbone CpG ODN (ODN-39M), forming high molecular weight aggregates. The evaluation of its immunogenicity in Balb/C mice revealed that only administration by intranasal route induced a systemic cross-reactive Cell-Mediated-Immunity (CMI). In turn, this combination was able to induce anti-N IgA in lungs, which along with the specific IgG in sera and CMI in spleen, resulted cross-reactive against the nucleocapsid protein of SARS-CoV-1. Furthermore, the nasal administration of the N+ODN-39M preparation combined with the RBD Delta protein, as inductor of neutralizing Abs, enhanced the local and systemic immune response against RBD with a modulation toward a Th1 pattern. Taken together, these results make the N+ODN-39M preparation a suitable component for a future intranasal pancorona vaccine against Sarbecoviruses. Particularly, the bivalent vaccine formulation N+ODN-39M+RBD could be used as an effective nasal booster in previously vaccinated population.

immunology↗