Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection

Johansen, Kari; Granqvist, L.; Karlén, K.; Stintzing, G; Uhnoo, Ingrid; Svensson, Lennart

doi:10.1007/bf01379129

Cited by 24 publications

(24 citation statements)

References 34 publications

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“…Johansen et al (19) established that after primary infection in humans serum IgA antibodies are mainly directed against VP2 and VP6. Similarly, Chang et al (6) measured isotypespecific ASC responses to individual RV structural and nonstructural proteins and observed that in all RV-inoculated piglets, VP6 induced the highest numbers of ASCs.…”

Section: Discussionmentioning

confidence: 99%

Magnitude of Serum and Intestinal Antibody Responses Induced by Sequential Replicating and Nonreplicating Rotavirus Vaccines in Gnotobiotic Pigs and Correlation with Protection

Azevedo

Yuan

Iosef

et al. 2004

Clin Vaccine Immunol

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A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. Because serum or fecal antibody titers, but not intestinal ASC responses, can be used as potential markers of protective immunity in clinical vaccine trials, we determined the serum and intestinal antibody responses to this prime-boost rotavirus vaccine regimen and the correlations with protection. Gnotobiotic pigs were vaccinated with one of the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were also compared with three i.n. doses of VLP؉mLT (VLP3x) Group A rotaviruses (RVs) are the most common dehydrating diarrheal agents of infants and young children worldwide (2, 4). Human RV (HRV) infections range from asymptomatic conditions to severe dehydrating gastroenteritis resulting in hospitalization and death (2, 4). Withdrawal of the live oral rhesus RV tetravalent vaccine (24) because of potential safety concerns (intussusception) has prompted the development and evaluation of recombinant nonreplicating candidate HRV vaccines. A sequential prime-boost vaccine regimen of priming with an oral HRV vaccine followed by intranasal (i.n.) boosting with RV protein VP2 and VP6 RV-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. However, priming and boosting with nonreplicating 2/6-VLPs did not provide protection (39). Data from previous studies with animals and humans have indicated a correlation between the titers of antibodies to RV in serum and the numbers of RV-specific ASCs in the intestinal tissues (5, 33) after RV infection. An earlier study with gnotobiotic pigs orally infected with the virulent Wa strain of HRV also showed that immunoglobulin A (IgA) ASC responses in intestinal tissues were correlated with serum IgA antibody responses (33), presumably reflecting the transit of intestinally derived IgA ASCs in the blood after RV infection. Furthermore, both intestinal IgA ASC numbers (in pigs) and serum IgA antibody titers (in pigs and humans) were correlated with protection against reinfection (33,35,43). However, similar correlates between antibody responses and protection have not been evaluated for nonreplicating i.n. RV vaccines or sequential prime-boost vaccine regimens with neonatal pigs or humans. Studies with adult mice showed that the protective immunity against RV infection elicited by 2/6-VLP or chimeric VP6 i.n. vaccines alone is not associated with induction of serum or intestinal RV antibodies (7,20,25). The discrepancies in the findings from...

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Section: Discussionmentioning

confidence: 99%

Magnitude of Serum and Intestinal Antibody Responses Induced by Sequential Replicating and Nonreplicating Rotavirus Vaccines in Gnotobiotic Pigs and Correlation with Protection

Azevedo

Yuan

Iosef

et al. 2004

Clin Vaccine Immunol

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“…To explore this, we generated fluorescent VLPs expressing the rotavirus VP2 (in fusion with eGFP) and VP6 proteins (19). Rotavirus VP2 and VP6 are highly immunogenic, and Abs, in particular, sIgA, toward these proteins are present in infected children (23)(24)(25). By ELISPOT we identified a small population (0.27% in the example reported in Fig.…”

Section: Selection Of Ag-specific Plasma Cellsmentioning

confidence: 99%

Rapid Generation of Rotavirus-Specific Human Monoclonal Antibodies from Small-Intestinal Mucosa

Niro

Mesin

Ráki

et al. 2010

The Journal of Immunology

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The gut mucosal surface is efficiently protected by Abs, and this site represents one of the richest compartments of Ab-secreting cells in the body. A simple and effective method to generate Ag-specific human monoclonal Abs (hmAbs) from such cells is lacking. In this paper, we describe a method to generate hmAbs from single Ag-specific IgA- or IgM-secreting cells of the intestinal mucosa. We found that CD138-positive plasma cells from the duodenum expressed surface IgA or IgM. Using eGFP-labeled virus-like particles, we harnessed the surface Ig expression to detect rotavirus-specific plasma cells at low frequency (0.03–0.35%) in 9 of 10 adult subjects. Single cells were isolated by FACS, and as they were viable, further testing of secreted Abs by ELISPOT and ELISA indicated a highly specific selection procedure. Ab genes from single cells of three donors were cloned, sequenced, and expressed as recombinant hmAbs. Of 26 cloned H chain Ab genes, 22 were IgA and 4 were IgM. The genes were highly mutated, and there was an overrepresentation of the VH4 family. Of 10 expressed hmAbs, 8 were rotavirus-reactive (6 with Kd < 1 × 10−10). Importantly, our method allows generation of hmAbs from cells implicated in the protection of mucosal surfaces, and it can potentially be used in passive vaccination efforts and for discovery of epitopes directly relevant to human immunity.

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“…It is also important to note that after RV infection, the predominant Ab response is directed against the two viral proteins (VP2 and VP6), which are the components of the GFP-VLPs (30).…”

Section: Immunofluorescent Staining and Confocal Microscopy Of Intestmentioning

confidence: 99%

Redundant Role of Chemokines CCL25/TECK and CCL28/MEC in IgA+ Plasmablast Recruitment to the Intestinal Lamina Propria After Rotavirus Infection

Feng

Jaimes

Lazarus

et al. 2006

The Journal of Immunology

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Rotaviruses (RV) are the most important cause of severe childhood diarrheal disease. In suckling mice, infection with RV results in an increase in total and virus-specific IgA+ plasmablasts in the small intestinal lamina propria (LP) soon after infection, providing a unique opportunity to study the mechanism of IgA+ cell recruitment into the small intestine. In this study, we show that the increase in total and RV-specific IgA+ plasmablasts in the LP after RV infection can be blocked by the combined administration of Abs against chemokines CCL25 and CCL28, but not by the administration of either Ab alone. RV infection in CCR9 knockout mice still induced a significant accumulation of IgA+ plasmablasts in the LP, which was blocked by the addition of anti-CCL28 Ab, confirming the synergistic role of CCL25 and CCL28. The absence of IgA+ plasmablast accumulation in LP following combined anti-chemokine treatment was not due to changes in proliferation or apoptosis in these cells. We also found that coadministration of anti-CCL25 and anti-CCL28 Abs with the addition of anti-α4 Ab did not further inhibit IgA+ cell accumulation in the LP and that the CCL25 receptor, CCR9, was coexpressed with the intestinal homing receptor α4β7 on IgA+ plasmablasts. Finally, we showed that RV infection was associated with an increase in both CCL25 and CCL28 in the small intestine. Hence, our findings indicate that α4β7 along with either CCR9 or CCR10 are sufficient for mediating the intestinal migration of IgA+ plasmablasts during RV infection.

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Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection

Cited by 24 publications

References 34 publications

Magnitude of Serum and Intestinal Antibody Responses Induced by Sequential Replicating and Nonreplicating Rotavirus Vaccines in Gnotobiotic Pigs and Correlation with Protection

Magnitude of Serum and Intestinal Antibody Responses Induced by Sequential Replicating and Nonreplicating Rotavirus Vaccines in Gnotobiotic Pigs and Correlation with Protection

Rapid Generation of Rotavirus-Specific Human Monoclonal Antibodies from Small-Intestinal Mucosa

Redundant Role of Chemokines CCL25/TECK and CCL28/MEC in IgA+ Plasmablast Recruitment to the Intestinal Lamina Propria After Rotavirus Infection

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