High Levels Of Serum Antibodies Research Articles

Chronic Infections and Atherosclerosis

The immune response against heat shock protein 60 (HSP60) derived from pathogens causing chronic infections is thought to be an important pro-atherogenic mechanism because high serum levels of antibodies against HSP60 have been associated with atherosclerotic diseases, such as coronary artery diseases, or cerebro-vascular events. Furthermore, the presence of HSP60-specific T lymphocytes in circulation may increase the risk of atherosclerosis. Our recent in vitro and in vivo studies have also shown an association of Helicobacter pylori-HSP60 (Hp-HSP60) specific Th1 immune responses elicited by H. pylori infection with the progression of atherosclerosis in a hyperlipidemic mouse model. These Th1 dominant immune responses may cross-react with endogenous HSP60 expressed on stressed cells of the vascular endothelium, likely due to molecular mimicry. However, the exact mechanisms by which endothelial cells display their HSP60 molecule or present HSP60 antigenic epitopes on the surface are still unclear.

Identification and Characterization of Novel Immunogenic Proteins of Streptococcus suis Serotype 2

Streptococcus suis, a zoonotic pathogen, caused serious outbreaks in humans with high mortality rates in the past decade. To develop safer and more effective vaccines, particularly for human protection, cell wall and extracellular proteins of S. suis serotype 2 were analyzed by an immunoproteomic approach in this study. Thirty-two proteins with high immunogenicity were identified and 22 of them were newly identified. Further analyses of 9 selected proteins revealed that (1) these 9 proteins were expressed in all tested virulent S. suis serotype 2 isolates, (2) antisera against 6 of the selected proteins efficiently killed the bacteria by opsonized phagocytosis in human blood, and (3) significantly higher levels of serum antibodies against 3 proteins were detected in both patients and infected swines. Therefore, our results suggest the 3 proteins (SSU98_0197, SSU98_1094 and SSU1664) have strong potential to be vaccine candidates.

Human papillomavirus and HPV vaccines: a review

Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.

Cervical cancer prevention strategies in the developing world

Cervical cancer prevention strategies in the developing world

High serum levels of antibodies against the recombinant 70 kDa ribonucleoprotein are useful for diagnosing mixed connective tissue disease

Anti-Sm antibodies and anti-RNP antibodies are considered to be diagnostic markers of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). However, cross-reactivity between the antibodies diminishes their discriminating specificity between these diagnoses. We examined whether we could achieve better differentiation between these two disease entities using recombinant antigens to RNP70 and SmD and quantitative immunoassays. Sera from 51 patients with SLE and 10 patients with MCTD and from a control group of 59 patients were used in a cross-sectional setting. Semiquantitative ELISAs for the detection of antibodies to RNP-70, RNP-A, RNP-C, SmBB' and SmD were used and the results were compared to conventional ELISA tests using U(1)-snRNP and a mixture of SmBB' and SmD as antigenic substrates. Sera from MCTD patients showed higher levels of anti-RNP-70 antibodies than sera from SLE patients. Levels of anti-SmBB' or anti-SmD antibodies were not significantly different between SLE and MCTD sera. However, the presence of antibodies directed against SmD was more frequent in SLE. Our results suggest that the use of RNP-70 and SmD antigens may increase the practical value of immunoassays used to confirm a diagnosis of SLE or MCTD in patients with connective tissue disease.

Comparative diagnostic potential of three serological tests for abortive Q fever in goat herds

Performances of an ELISA, an immunofluorescence assay (IFA) and a complement fixation test (CFT) were assessed for detecting antibodies against Coxiella burnetii after Q fever abortions in naturally infected goats. The goal of the study was to provide information useful for veterinary serodiagnosis in regard to categories of goats either experiencing Q fever abortion or not, blood sampling times and recommended cut-offs. The study was conducted on eight goat herds with evidence of C. burnetii abortions. In each herd, at least 5 goats that had aborted and 10 goats prior to parturition or at term were monitored 15, 30 and 60 days (D15, D30, D60) after the onset of Q fever abortion. The overall CFT results distribution did not differ between the two groups of goats and showed poor agreement with the ELISA results. In contrast, the ELISA and IFA results revealed comparable significant differences, but overall the ELISA test was slightly more sensitive than the IFA test. Seroprevalence, according to ELISA and IFA respectively, was higher in the aborting (88% and 82%) than in the non-aborting group (60% and 50%). High levels of serum antibodies were detected in goats post-abortion with an average of 114 %OD using ELISA and a log 10(titer) of 2.4 using IFA. Strongly positive ELISA (%OD > 80) and positive IFA results (log 10(titers) > 1.9) were significantly associated with abortion. Sampling on D15 gave the best association with ORs of 10 for ELISA and 6 for IFA. The practical interest of these results is discussed.

Analysis of Immunoprotectivity of the Recombinant OmpA of Rickettsia heilongjiangensis

A truncated gene ompA was amplified from Rickettsia heilongjiangensis isolated in China and a 56-kDa truncated OmpA protein was expressed in E. coli cells transformed with the ompA-recombined expression plasmid. High levels of serum antibodies to R. heilongjiangensis and proliferation of the splenic cells were found in mice immunized with the truncated OmpA. After challenge with R. heilongjiangensis or R. rickettsii, fever and pathological damages of the guinea pigs immunized with the truncated OmpA were significantly slighter as compared with those of nonimmunized guinea pigs. These results suggest that the truncated OmpA of R. heilongjiangii is immunogenic for effectively inducing humoral and cell-mediated immune responses against homologous and heterologous species in the spotted fever group.

High levels of serum antibodies to merozoite surface protein 2 of Plasmodium falciparum are associated with reduced risk of clinical malaria in coastal Kenya

The merozoite surface protein (MSP) 2 is a vaccine candidate antigen of Plasmodium falciparum that is polymorphic in natural populations. In a prospective cohort study in two coastal populations of Kenya using recombinant proteins derived from the two major allelic types of MSP2, high serum levels of IgG to MSP2 were associated with protection from clinical malaria. This protection was independent of that associated with antibodies to another vaccine candidate antigen (AMA1) in these populations. However, low antibody levels to MSP2 appeared to be associated with increased susceptibility to malaria within people who were parasite negative at the time of serum collection. These data suggest that an MSP2 based vaccine should be designed to induce high level antibody responses against the different MSP2 types present globally in P. falciparum populations and that MSP2 could be combined with other P. falciparum antigens to form a multi-component malaria vaccine.

1128. Ad-sig-TAA/ecdCD40L Vector Prime, TAA/CD40L Protein Boost Vaccine Breaks Tolerance for Tumor Assoicated Antigens (TAA) and Suppresses Growth and Metastasis of Epithelial Neoplastic Cells

In order to develop a method to overcome the immune tolerance of cancer, we have designed an adenoviral vector, designated Ad-sig-TAA/ecdCD40L, which carries a transcription unit encoding the extracellular domain (ecd) of the CD40 ligand (CD40L) linked to TAA. The TAA are in turn linked to a secretory signal peptide (sig). This work was based on earlier DNA vaccines reported by Ralph Reisfeld. The binding of the CD40L to the CD40 receptor on DCs activates them. The binding of the TAA/CD40L chimeric protein leads to the internalization of the TAA and its ultimate presentation of Class I MHC on the DCs. In vivo and in vitro analysis showed that the subcutaneous injection of the Ad-sig-TAA/ecdCD40L adenoviral vector led to the development of a CD8+ T cell lymphocyte systemic immune response against TAA for up to a year. One of the TAA tested is MUC-1, which is overexpressed in epithelial cancer cells. We have shown that the Ad-sig-ecdhMUC-1/ecdCD40L vector makes the hMUC-1.Tg mice (which otherwise are killed by the growth of hMUC-1 positive cancer cell lines) resistant to the engraftment and growth of a hMUC-1 positive cancer cell line. In contrast, the cancer cell line which lacks the hMUC-1 antigen engrafts and grows well in these transgenic mice. We have also shown that subcutaneous injections of the hMUC-1/ecdCD40L protein following the vector injection increase the level of the hMUC-1 specific T cells, and generates high levels of serum antibodies against the hMUC-1 antigen. Importantly, these antibodies bind to breast and prostate cancer cancer cells in biopsy specimens from human subjects. The target of these antibodies is a 20 amino acid repeat in the MUC-1 extracellular domain which can completely block the binding of the antibodies to the human breast cancer epithelial cells in biopsy specimens. The schedule of one subcutaneous (sc) injection of the Ad-sig-MUC-1/ecdCD40L vector followed in 7 and 14 days by a sc injection of the MUC-1/ecdCD40L protein is the best schedule among many other combinations and schedules tested. In addition to the MUC-1 self antigen, we have tested the Ad-sig-rH2N/ecdCD40L vector which contains the rat her-2-neu (rH2N) antigen. We tested this vaccine in rH2N.Tg mice which are anergic to the rH2Nantigen. We found that one sc injection of the Ad-sig-rH2N/ecdCD40L vector followed by 2 sc injections of the rH2N/ecdCD40L protein breaks tolerance which exists in the rH2N.Tg mice which are otherwise tolerant of the rH2N TAA. This Ad-sig-TAA/ecdCD40L vector strategy outperforms both corresponding DNA vaccines as well as cellular based cytokine modified tumor cell vaccines. We plan to complete the preclinical testing necessary to bring this new strategy into phase I toxicity testing in the near future.

W13-P-015 High serum antibody levels toperiodontal pathogens are associated with subclinical, prevalent, and future CHD

W13-P-015 High serum antibody levels toperiodontal pathogens are associated with subclinical, prevalent, and future CHD

Serum Antibody Levels to Actinobacillus actinomycetemcomitans Predict the Risk for Coronary Heart Disease

The association between serum antibody levels to major periodontal pathogens and coronary heart disease (CHD) was analyzed in a prospective population-based study. The population comprised 1023 men (aged 46 to 64 years) in the Kuopio Ischemic Heart Disease Study. The subjects with CHD at baseline (n=113) were more often seropositive for Porphyromonas gingivalis IgA (38.9% versus 28.5%, P=0.021) and IgG (60.2% versus 46.7%, P=0.007) than those without CHD. During the 10-year follow-up, 109 men free from CHD at baseline experienced an acute myocardial infarction or CHD death. The men with an end point were more often seropositive for Actinobacillus actinomycetemcomitans IgA (15.5% versus 10.2%, P=0.019) than those who remained healthy. In the highest tertile of A. actinomycetemcomitans IgA-antibodies compared with the lowest one, the relative risk (RR) for an end point adjusted for CHD risk factors was 2.0 (95% confidence interval [CI], 1.2 to 3.3). In the Porphyromonas gingivalis IgA-antibody tertiles, the highest RR of 2.1 (1.3 to 3.4) was observed in the second tertile. All antibody levels correlated positively with the carotid artery intima-media thickness. High-serum antibody levels to major periodontal pathogens are associated with subclinical, prevalent, and future incidence of CHD. Periodontal pathogens or host response against them may contribute to the pathogenesis of CHD.

Dietary 18:3ω3 influences immune function and the tissue fatty acid response to antigens and adjuvant

α-Linolenic acid (18:3ω3) has many important physiological functions including being β-oxidized, serving a precursor to the synthesis of other lipids and it has immunomodulation properties. The objective of the present study was to test the effects of immunization and dietary 18:3ω3 on immune function and the fatty acid profile of immunized pig tissues. Piglets suckled from sows consuming either a control or high 18:3ω3 diet until 14 days old when they were weaned onto a similar diet as the sow and were moved to a segregated nursery for the remainder of the study. At 35 days of age, pigs on both diets (2 × 2 factorial design) received either an injection containing hen eggwhite lysozyme (HEWL), killed Mycobacterium tuberculosis and Freund’s complete adjuvant (immunized) or phosphate buffered saline (PBS) (non-immunized) into the neck followed by a booster injection 2 weeks later and induction of delayed-type hypersensitivity (DTH) one week later. Immunization increased (compared to non-immunized) while the high 18:3ω3 diet decreased haptoglobin by 30% compared to pigs consuming the control diet. Immunized pigs had a seven-fold increase in antibodies to HEWL and pigs consuming the high 18:3ω3 diet also had transiently higher levels of serum antibodies. There was a diet by immunization interaction on the DTH reaction such that immunized pigs consuming the high 18:3ω3 had the largest DTH reaction. The neck muscle proximal to the site of injection of immunized pigs had 10–30% lower levels of triglyceride and phospholipid linoleic (18:2ω6) and 18:3ω3 compared to non-immunized pigs. Thus, a high 18:3ω3 intake in pigs modulates immune function and tissue fatty acids in response to immunization.

Decreased serum and pharyngeal antibody levels specific to streptococcal lipoteichoic acid in children with recurrent tonsillitis

Objective: Streptococcus ( S.) pyogenes is a common cause of primary as well as recurrent tonsillitis (RT). Lipoteichoic acid (LTA) has been proposed as a possible candidate for vaccine formulation against streptococcal infections, because LTA is a common constituent of streptococci and the antibody to LTA inhibits bacterial attachment to epithelial cells in vitro. Streptolysin-O and streptococcal whole cell body are highly immunogenic and the antibodies to these antigens are reported to be better parameters for streptococcal infections The objective of the present study is to investigate how systemic and local immune activities against S. pyogenes may be associated with RT. Methods: Sera from 178 children with or without RT aged 1–15 years with a median age of 5 years were investigated for the levels of total immunoglobulins and antibodies specific to streptococcal antigens such as whole cell body, LTA, and streptolysin-O. Pharyngeal secretions from 67 children with or without RT aged 2–14 years with a median age of 6 years were subjects to secretory IgA (SIgA) antibody levels to streptococcal LTA. The antibodies to whole cell body and LTA were measured by enzyme-linked immunosorbent assay. Total immunoglobins and the anti-streptolysin-O antibody were assayed by nephelometry. Results: An age-matched comparison revealed that either levels of serum IgG antibody or pharyngeal SIgA antibody to streptococcal LTA at 2–5 years of age were significantly lower in RT children than in non-RT children (1.39 vs. 5.14 μg/ml, P=0.001; 10.6 vs. 29.9 units/ng/ml total SIgA, P=0.015; respectively) and correlated inversely to episodes of tonsillitis ( r=−0.242, P=0.024; r=−0.3, P=0.024; respectively). Either serum total immunoglobulin levels of IgG or IgA correlated positively to episodes of tonsillitis in children aged 2–5 years ( r=0.293, P=0.011; r=0.361, P=0.002; respectively). No difference was found on either serum levels of IgG antibody to streptococcal whole cell body or antibody to streptolysin-O between RT and non-RT children in any age-matched comparisons. High serum antibody levels to whole cell body was associated with high antibody levels to streptococcal LTA in non-RT children ( r=0.198, P<0.05), but no association was found between these antibody levels in RT children. Conclusions: Selective immunologic failure in systemic and pharyngeal antibody response to streptococcal LTA may be a potential cause of RT in young children.

Neisseria meningitidis RTX protein FrpC induces high levels of serum antibodies during invasive disease: polymorphism of frpC alleles and purification of recombinant FrpC.

The Neisseria meningitidis FAM20 strain secretes two proteins of unknown function, FrpA and FrpC, which contain typical RTX domains found in cytotoxins from other gram-negative pathogens. To evaluate whether the Frp proteins could be involved in meningococcal virulence, 65 isolates of all serogroups were screened by PCR for the presence of both frp genes. The frpA allele was, however, poorly conserved. A single strain harbored an frpA allele of the previously described size, while large insertions were detected in the frpA loci of 22 isolates (34%), and the 42 remaining isolates (65%) did not contain frpA at all. In contrast, frpC alleles, albeit of variable length, were detected in all invasive and most carrier strains. This suggests that meningococci may produce a family of FrpC proteins of various molecular masses. High levels of both immunoglobulin G (IgG) and IgA class antibodies recognizing recombinant FrpC were indeed detected in convalescent-phase sera of most patients at 2 and 4 to 5 weeks after the first symptoms of meningococcal disease. These results show that FrpC-like proteins are produced and may play a role in invasive meningococcal infections.

H. pylori and functional dyspepsia: increased serum antibodies as an independent risk factor?

The relationship between H. pylori and functional dyspepsia is controversial. Hypothesizing that subjects with a more intense immune response to H. pylori (and hence higher antibody titers) would be at greater risk of dyspepsia, we aimed to identify risk factors for the development of dyspeptic symptoms. In all, 491 healthy blood donors with no history of peptic ulceration and 74 consecutive patients with a confirmed diagnosis of functional dyspepsia were studied. Symptoms and potential risk factors [nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, and smoking] were measured by a validated questionnaire. H. pylori status was determined by IgG antibodies using a validated ELISA test with a cutoff titer for a positive serology of 10 units/ml. Logistic regression analysis assessed the association between risk factors and dyspepsia. Among blood donors, 21% (95% CI 17.6-24.8) reported dyspepsia (pain localized to the upper abdomen); 7.7% (95% CI 5.5-10.4) had frequent dyspepsia (>6 times in the prior year). The age-adjusted prevalence of H. pylori was not significantly different in blood donors with (39.5%, 95% CI 24.0-56.6) and without frequent dyspepsia (34.2%, 95% CI 29.8-38.36), but was significantly greater in patients with functional dyspepsia (68.8%, 95% CI 57.3-77.9). In the combined study population of blood donors and patients with functional dyspepsia, logistic regression adjusting for age identified the following independent risk factors for frequent dyspepsia: high serum antibody levels against H. pylori (OR for IgG titer >50 units/ml vs H. pylori titers 11-50 units/ml 4.6, 95% CI 2.7-7.8) and consumption of standard NSAIDs (OR 2.4,95% CI 1.3-4.5). In contrast, alcohol (OR 0.6, 95% CI 0.3-1.0), smoking (OR 1.5, 95% CI 1.0-2.3) or positive H. pylori serology with titers < or = 50 units/ml (OR 1.6, 95% CI 0.8-2.9) were not associated with frequent dyspepsia. In conclusion, in a subgroup of H. pylori-infected subjects who have high antibody titers, H. pylori appears to be associated with functional dyspepsia.

A DNA vaccine encoding a conserved Eimeria protein induces protective immunity against live Eimeria acervulina challenge

Coccidiosis is caused by several distinct intestinal protozoa of Eimeria sp., and is responsible for intestinal lesions and severe body weight loss in chickens. To develop a DNA vaccination strategy for coccidiosis, an expression vector pMP13 encoding a conserved antigen of Eimeria was constructed by subcloning 3-1E cDNA into pBK-CMV and used to elicit protective immunity against E. acervulina. One-day-old chickens were immunized intramuscularly (IM) or subcutaneously (SC) with various doses of pMP13 expression vector ranging from 5 to 100 ug two weeks apart and were challenged with 5×10 3 E. acervulina. Chickens immunized with 5, 10, 50 or 100 ug of pMP13 plasmid, but not control plasmid, pBK-CMV, showed significantly reduced oocysts following challenge infection with E. acervulina. Two injections were in general more effective than one injection with higher dose of DNA eliciting better protection. At 10 days post challenge infection, maximum levels of circulating antibodies were detected regardless of the routes of injection, although IM injection provided higher levels of serum antibodies compared to SC injection. Serum antibody levels demonstrated a dose-dependent response showing higher antibody production at higher DNA dose. DNA immunization with pMP13 also induced significant changes in T-cell subpopulations in the spleen and duodenum intraepithelial lymphocytes. At 4 days post DNA immunization, pMP13-immunized chickens showed lower CD8, and higher CD4 + and γδ T + cells in the duodenum compared to the pBK-CMV-immunized chickens. Following challenge infection with E. acervulina, pMP13-immunized chickens showed lower CD8 + and αβ T + cells, and higher CD4 + cells than pBK-CMV-immunized chickens in the duodenum. These findings demonstrate that DNA immunization with pMP13 induce local and systemic host immune responses against Eimeria.

Structure and serologic properties of O-specific polysaccharide from Citrobacter freundii possessing cross-reactivity with Escherichia coli O157:H7.

Citrobacter freundii OCU158 is a serologically cross-reactive strain with Escherichia coli O157:H7. To explore the close relationship between two strains, we have analyzed the chemical structures of O-specific polysaccharides and antigenic properties of lipopolysaccharides (LPSs) of both strains. The structure of O-specific polysaccharides from both strains was found to be identical by chemical and nuclear magnetic resonance analyses, in which D-PerNAc was 4-acetamido-4,6-dideoxy-D-mannose: [-->4)-beta-D-Glc-(1-->3)-alpha-D-PerNAc-(1-->4)-alpha-D-GalNAc-(1 --> 3)-alpha-L-Fuc-(1-->](n). The enzyme immunoassay using LPS derived either from E. coli O157 or from C. freundii could equally detect high levels of serum antibodies against LPS in patients with enterohemorrhagic E. coli (EHEC) O157 infection. Absorption of antibodies in EHEC patient serum by LPS from E. coli O157 or C. freundii, however, showed a difference in the epitopes. This difference was attributable to the epitope specificity of the core region and/or lipid A structure in LPS.

Structure and serologic properties of O-specific polysaccharide from Citrobacter freundii possessing cross-reactivity with Escherichia coli O157:H7

Citrobacter freundii OCU158 is a serologically cross-reactive strain with Escherichia coli O157:H7. To explore the close relationship between two strains, we have analyzed the chemical structures of O-specific polysaccharides and antigenic properties of lipopolysaccharides (LPSs) of both strains. The structure of O-specific polysaccharides from both strains was found to be identical by chemical and nuclear magnetic resonance analyses, in which D-PerNAc was 4-acetamido-4,6-dideoxy- D-mannose: [→4)-β- D-Glc-(1→3)-α- D-PerNAc-(1→4)-α- D-GalNAc-(1→3)-α- L-Fuc-(1→] n. The enzyme immunoassay using LPS derived either from E. coli O157 or from C. freundii could equally detect high levels of serum antibodies against LPS in patients with enterohemorrhagic E. coli (EHEC) O157 infection. Absorption of antibodies in EHEC patient serum by LPS from E. coli O157 or C. freundii, however, showed a difference in the epitopes. This difference was attributable to the epitope specificity of the core region and/or lipid A structure in LPS.

Protection of the villus epithelial cells of the small intestine from rotavirus infection does not require immunoglobulin A.

Immunoglobulin A (IgA) is the primary immune response induced in the intestine by rotavirus infection, but vaccination with virus-like particles induces predominantly IgG, not IgA. To definitively assess the role of IgA in protection from rotavirus infection, IgA knockout mice, which are devoid of serum and secretory IgA, were infected and then rechallenged with murine rotavirus at either 6 weeks or 10 months. Following primary rotavirus infection, IgA knockout mice cleared virus as effectively as IgA normal control mice. Rotavirus-infected IgA knockout mice produced no serum or fecal IgA but did have high levels of antirotavirus serum IgG and IgM and fecal IgG, whereas IgA normal control mice made both serum IgA and IgG and fecal IgA. Both IgA normal and IgA knockout mice were totally protected from rotavirus challenge at 42 days. Ten months following a primary infection, both IgA normal and knockout mice still had high levels of serum and fecal antirotavirus antibody and were totally protected from rotavirus challenge. To determine if compensatory mechanisms other than IgG were responsible for protection from rotavirus infection in IgA knockout mice, mice were depleted of CD4(+) T cells or CD8(+) T cells. No changes in the level of protection were seen in depleted mice. These data show that fecal or systemic IgA is not essential for protection from rotavirus infection and suggest that in the absence of IgA, IgG may play a significant role in protection from mucosal pathogens.

Do we need 3 doses of hepatitis B vaccine?

The hepatitis B virus (HBV) vaccine may provide protection through the clonal expansion of specific memory cells without necessarily having to produce high serum antibody levels. We develop a mathematical model which distinguishes between the accumulation of sensitive memory B and T-helper cells prior to a booster and the high circulating antibody levels present in an individual after a booster. We suggest this immune memory accumulates primarily in an antigen-independent fashion. These phenomena suggest individuals may be immune to infection six months after the priming vaccine dose(s) regardless of whether they receive a booster or not. This hypothesis is supported by immunogenicity data and by two independent vaccine efficacy trials comparing 0, 1 month schedules with 0, 1 and 6 month schedules.