Polarizing T and B Cell Responses by APC-Targeted Subunit Vaccines

Grødeland, Gunnveig; Fossum, Even; Bogen, Bjarne

doi:10.3389/fimmu.2015.00367

Cited by 45 publications

(39 citation statements)

References 77 publications

(102 reference statements)

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“…However, previous reports have shown that several of the targeting units used in this study (aMHCII, Xcl1, MIP1-a, aCD40) enhanced T cell responses (8,9,11,13,18,19). Thus, the relatively selective IgG2a responses elicited by Xcl1, MIP-1a, and aCD40 targeting correlated with increased Th1 responses (9,11,18,19), whereas the mixed IgG1/2a responses induced by aMHCII targeting was associated with a mixed Th1/2 profile (18,24). Thus, for the novel specificities, it is likely that GM-CSF induces predominantly a Th2 response, aDEC205 a Th1 response, whereas aCD11c, FliC, and Flt-3L elicit a mixed Th1/2 response.…”

Section: Discussioncontrasting

confidence: 41%

The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules

et al. 2018

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Upon APC-targeted DNA vaccination, transfected cells secrete fusion proteins with targeting units specific for surface molecules on APC. In this study, we have tested several different targeting units for their ability to influence the magnitude and subclass of Ab responses to hemagglutinin from influenza A virus. The experiments employed bivalent homodimeric Ig-based molecules (vaccibodies). The overall efficiency in BALB/c mice depended on the targeting units in the following order: αMHC class II > αCD11c > αCD40 > Xcl-1 = MIP-1α > FliC > GM-CSF > Flt-3L > αDEC205. GM-CSF induced mainly IgG1, whereas Xcl1, MIP-1α, αCD40, and αDEC205 induced predominantly IgG2a. A more balanced mixture of IgG1 and IgG2a was observed with αCD11c, αMHC class II, Flt-3L, and FliC. Similar results of IgG subclass–skewing were obtained in Th1-prone C57BL/6 mice with a more limited panel of vaccines. IgG1 responses in BALB/c occurred early after immunization but declined relatively rapidly over time. IgG2a responses appeared later but lasted longer (>252 d) than IgG1 responses. The most efficient targeting units elicited short- and long-term protection against PR8 influenza (H1N1) virus in BALB/c mice. The results suggest that targeting of Xcr1+ conventional type 1 dendritic cells preferentially induces IgG2a responses, whereas simultaneous targeting of several dendritic cell subtypes also induces IgG1 responses. The induction of distinct subclass profiles by different surface molecules supports the APC–B cell synapse hypothesis. The results may contribute to generation of more potent DNA vaccines that elicit high levels of Abs with desired biologic effector functions.

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Section: Discussioncontrasting

confidence: 41%

The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules

et al. 2018

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“…routes induced both IgG1 and IgG2a JEV‐specific antibody responses, IgG2a titers being 1.5‐fold higher than IgG1 titers (Fig. ), indicating good induction of a Th1 cell response . By contrast, MVA‐vJH6 immunization s.l.…”

Section: Resultsmentioning

confidence: 96%

“…generated titers of IgG1 that were approximately twice those of IgG2a, indicating that the Th2 cell response was stronger (Fig. ) . However, both vaccine types administered via s.l.…”

Section: Resultsmentioning

confidence: 96%

Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice

Lee

Kim

Lee

et al. 2016

Microbiology and Immunology

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The Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis. Although there are four classes of vaccines against JEV, all of them are administered by s.c or i.m injection. Here, the effectiveness of sublingual (s.l.) administration of a JEV live-attenuated vaccine or recombinant modified vaccinia virus Ankara (MVA) vaccine, including JEV prM/E, was investigated. The mice were immunized three times i.m. or s.c. One week after the final immunization by both s.l. and i.m. routes, the titers of IgG1 induced by the recombinant MVA vaccine were higher than those induced by the live-attenuated vaccine, whereas the titers of IgG2a induced by the live-attenuated vaccine were higher than those induced by the recombinant MVA vaccine. However, both vaccines induced neutralizing antibodies when given by either s.l. or i.m. routes, indicating that both vaccines induce appropriate Th1 and Th2 cell responses through the s.l. and i.m. routes. Moreover, both vaccines protected against induction of proinflammatory cytokines and focal spleen white pulp hyperplasia after viral challenge. Virus-specific IFN-γ CD4 and CD8 T cells appeared to increase in mice immunized via both s.l. and i.m. routes. Interestingly, virus-specific IL-17 CD4 T cells increased significantly only in the mice immunized via the s.l. route; however, the increased IL-17 did not affect pathogenicity after viral challenge. These results suggest that s.l. immunization may be as useful as i.m. injection for induction of protective immune responses against JEV by both live-attenuated and recombinant MVA vaccines.

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“…The UV-inactivated SARS coronavirus vaccine retained its immunogenicity and promoted Th2type immune responses (Tsunetsugu-Yokota et al 2007). The activation of Th2 responses such as IL-10 stimulate B cell proliferation, which can produce specific and nonspecific anti-infection antibodies (Grodeland et al 2015); similarly, both T and B cells have functions following Lactobacillus vaccination. The production of IL-9 by Th2 cells results in the proliferation of mast cell growth, and IL-13 stimulates epithelial cell growth (Tukler Henriksson et al 2015).…”

Section: Discussionmentioning

confidence: 99%

A phase trial of the oral Lactobacillus casei vaccine polarizes Th2 cell immunity against transmissible gastroenteritis coronavirus infection

Jiang

Hou

Tang

et al. 2016

Appl Microbiol Biotechnol

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Transmissible gastroenteritis coronavirus (TGEV) is a member of the genus Coronavirus, family Coronaviridae, order Nidovirales. TGEV is an enteropathogenic coronavirus that causes highly fatal acute diarrhoea in newborn pigs. An oral Lactobacillus casei (L. casei) vaccine against anti-transmissible gastroenteritis virus developed in our laboratory was used to study mucosal immune responses. In this L. casei vaccine, repetitive peptides expressed by L. casei (specifically the MDP and tuftsin fusion protein (MT)) were repeated 20 times and the D antigenic site of the TGEV spike (S) protein was repeated 6 times. Immunization with recombinant Lactobacillus is crucial for investigations of the effect of immunization, such as the first immunization time and dose. The first immunization is more important than the last immunization in the series. The recombinant Lactobacillus elicited specific systemic and mucosal immune responses. Recombinant L. casei had a strong potentiating effect on the cellular immunity induced by the oral L. casei vaccine. However, during TGEV infection, the systemic and local immune responses switched from Th1 to Th2-based immune responses. The systemic humoral immune response was stronger than the cellular immune response after TGEV infection. We found that the recombinant Lactobacillus stimulated IL-17 expression in both the systemic and mucosal immune responses against TGEV infection. Furthermore, the Lactobacillus vaccine stimulated an anti-TGEV infection Th17 pathway. The histopathological examination showed tremendous potential for recombinant Lactobacillus to enable rapid and effective treatment for TGEV with an intestinal tropism in piglets. The TGEV immune protection was primarily dependent on mucosal immunity.

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Polarizing T and B Cell Responses by APC-Targeted Subunit Vaccines

Cited by 45 publications

References 77 publications

The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules

The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules

Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice

A phase trial of the oral Lactobacillus casei vaccine polarizes Th2 cell immunity against transmissible gastroenteritis coronavirus infection

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