Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles

Ogier, Agathe; Franco, Manuel; Charpilienne, Annie; Cohen, Jean; Pothier, Pierre; Kohli, Évelyne

doi:10.1002/eji.200526059

Cited by 16 publications

(22 citation statements)

References 31 publications

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“…A similar profile has been reported for RV-specific B cells during natural RV infection in children (23). By contrast, it was recently shown that intranasal immunization with 2/6-VLP did not induce a significant number of RV-specific B cells with an intestinal homing profile (38). In our model, most of our vaccine regimens induced coproantibodies to RV.…”

Section: Vol 80 2006 Rectal Immunization With Rv Vlp In Mice 1757mentioning

confidence: 58%

Rectal Immunization with Rotavirus Virus-Like Particles Induces Systemic and Mucosal Humoral Immune Responses and Protects Mice against Rotavirus Infection

Parez

Fourgeux

Mohamed

et al. 2006

J Virol

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To evaluate whether the rectal route of immunization may be used to provide appropriate protection against enteric pathogens such as rotaviruses (RV), we studied the antibody response and the protection induced by rectal immunization of mice with RV virus-like particles (VLP). For this purpose, 6-week-old BALBc mice were rectally immunized twice with RV 8-2/6/7-VLP derived from the bovine RV RF81 strain either alone or combined with various adjuvants including four toxins [cholera toxin (CT) and three attenuated Escherichia coli-derived heat-labile toxins (LTs), LT(R192G), LT(R72), and LT ( Rotaviruses (RV) are the leading cause of viral gastroenteritis in young children worldwide and are responsible for more than 500,000 deaths per year in developing countries (40). The high mortality rate in developing countries and the heavy social and economical burden in industrialized countries due to RV infections underline the need for the development of an efficient vaccine. Every candidate RV vaccine that has been developed to date has consisted of orally delivered, live attenuated RV strains or reassortants (8,9,14,20,36,54,56). Most of these vaccines confer significant protection against severe diarrhea but only limited protection against RV infection or mild symptoms. Moreover, live vaccines can be associated with various adverse effects, intussusception being the most severe (33). Thus, the development of new safe vaccine strategies based on nonliving RV should be considered.Virus-like particles (VLP) are nonreplicating structures that mimic virus counterparts in morphology and immunogenicity and could be safe and efficient vaccine candidates. Parenteral immunization with RV VLP has been shown to induce immunogenicity and protection in animal models, particularly in the mouse model (7,11,30). However, RV is commonly transmitted via the fecal-oral route and infects intestinal epithelial cells. Thus, vaccine strategies inducing effective intestinal mucosal immunity responses should be suitable against this pathogen and need to be assessed. RV VLP can be delivered via various mucosal routes of administration in order to induce mucosal effectors. When delivered via the oral route, which is common and handy for vaccine administration, RV VLP induce weak immune responses and do not protect against infection (3, 49). When administered by the nasal route, RV VLP efficiently induce both local and systemic specific immune responses in mice (6,29,34,35) and gnotobiotic pigs (21).

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Section: Vol 80 2006 Rectal Immunization With Rv Vlp In Mice 1757mentioning

confidence: 58%

Rectal Immunization with Rotavirus Virus-Like Particles Induces Systemic and Mucosal Humoral Immune Responses and Protects Mice against Rotavirus Infection

Parez

Fourgeux

Mohamed

et al. 2006

J Virol

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“…More recently, a study with mice showed that i.n. immunization with 2/6-VLPs induced a high frequency of RV-specific B cells in the respiratory lymphoid tissue and spleen, but only a minor fraction of them expressed the ␣ 4 ␤ 7 integrin (40). Taken together, these results may explain why the administration of antigens by the i.n.…”

Section: Discussionmentioning

confidence: 81%

Intrarectal Immunization with Rotavirus 2/6 Virus-Like Particles Induces an Antirotavirus Immune Response Localized in the Intestinal Mucosa and Protects against Rotavirus Infection in Mice

Agnello

Hervé

Lavaux

et al. 2006

J Virol

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Rotavirus (RV) is the main etiological agent of severe gastroenteritis in infants, and vaccination seems the most effective way to control the disease. Recombinant rotavirus-like particles composed of the viral protein 6 (VP6) and VP2 (2/6-VLPs) have been reported to induce protective immunity in mice when administered by the intranasal (i.n.) route. In this study, we show that administration of 2/6-VLPs by the intrarectal (i.r.) route together with either cholera toxin (CT) or a CpG-containing oligodeoxynucleotide as the adjuvant protects adult mice against RV infection. Moreover, when CT is used, RV shedding in animals immunized by the i.r. route is even reduced in comparison with that in animals immunized by the i.n. route. Humoral and cellular immune responses induced by these immunization protocols were analyzed. We found that although i.r. immunization with 2/6-VLPs induces lower RV-specific immunoglobulin G (IgG) and IgA levels in serum, intestinal anti-RV IgA production is higher in mice immunized by the i.r. route. Cellular immune response has been evaluated by measuring cytokine production by spleen and Peyer's patch cells (PPs) after ex vivo restimulation with RV. Mice immunized by the i.n. and i.r. routes display higher gamma interferon production in spleen and PPs, respectively. In conclusion, we demonstrate that i.r. immunization with 2/6-VLPs protects against RV infection in mice and is more efficient than i.n. immunization in inducing an anti-RV immune response in intestinal mucosa.

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“…RV infects mature enterocytes of the small intestine causing gastroenteritis and represents a good viral model of mucosal infection and thus of mucosal immunization. In a previous work [4], we used the same method as Youngman et al [3], based on RV GFP-virus-like particle (VLP) binding, to trace RV-specific B cell responses in respiratory and intestinal lymphoid tissues after intranasal (IN) immunization of mice with VLP in the presence of mucosal adjuvant. This strategy has been shown to confer protection against RV infection [5].…”

Section: Introductionmentioning

confidence: 99%

Distribution and phenotype of rotavirus-specific B cells induced during the antigen-driven primary response to 2/6 virus-like particles administered by the intrarectal and the intranasal routes

Martino

Basset

Ogier

et al. 2007

Journal of Leukocyte Biology

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Selection of mucosal sites is an important step in mucosal vaccine development. The intrarectal (IR) route represents an alternative to the oral route of immunization; nevertheless, immune responses induced by this route are not well defined. Here, we studied the early primary B cell response (induction, homing, and phenotype) induced by IR immunization with rotavirus (RV)-2/6 virus-like particles (VLP). Using flow cytometry, we traced RV-specific B cells in different lymphoid tissues and analyzed the expression of alpha4beta7 and CCR9, which are important receptors for homing to the gut, as well as CD5, a marker expressed by B1-a cells, which are a major source of natural antibodies. We observed a massive, specific B cell response in rectal follicles, lumbar, and mesenteric lymph nodes but not in Peyer's patches or cervical lymph nodes. A minority of cells expressed alpha4beta7, suggesting a probable lack of migration to the gut, whereas CCR9 and CD5 were expressed by 30-50% and 30-75% of specific B cells, respectively. Then, we compared the intranasal route of immunization and observed similar B cell frequency and phenotype but in respiratory lymphoid tissues. These results confirm the high compartmentalization of B cell responses within the mucosal system. They show that CCR9 expression, conversely to alpha4beta7, is not restricted to B cells induced in the gut. Finally, an important part of the RV-specific B cell response induced at the mucosal level during the primary response to VLP is most likely a result of B1-a cells.

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Distribution and phenotype of murine rotavirus-specific B cells induced by intranasal immunization with 2/6 virus-like particles

Cited by 16 publications

References 31 publications

Rectal Immunization with Rotavirus Virus-Like Particles Induces Systemic and Mucosal Humoral Immune Responses and Protects Mice against Rotavirus Infection

Rectal Immunization with Rotavirus Virus-Like Particles Induces Systemic and Mucosal Humoral Immune Responses and Protects Mice against Rotavirus Infection

Intrarectal Immunization with Rotavirus 2/6 Virus-Like Particles Induces an Antirotavirus Immune Response Localized in the Intestinal Mucosa and Protects against Rotavirus Infection in Mice

Distribution and phenotype of rotavirus-specific B cells induced during the antigen-driven primary response to 2/6 virus-like particles administered by the intrarectal and the intranasal routes

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