IgG Subclass Antibodies Research Articles

Immune responses to birch in young children during their first 7 years of life.

The character of immune responses to allergens during the first years of life may decide whether the individual will become tolerant or develop allergy later in life. To study the development of immune responses to the seasonal inhalant allergen birch over the first 7 years of life. Blood samples were obtained from 21 children who were followed prospectively from the second to the seventh pollen season of life. Birch-induced cytokine production and IgG subclass antibodies to rBet v 1 were analysed with ELISA, mRNA expression with real time PCR, IgE antibodies to birch with Magic Lite and birch-induced mononuclear cell proliferation with 3H-thymidine incorporation. Birch-induced IFN-gamma and IL-10 production increased with age, both in atopic and non-atopic children, while birch-induced IL-13 production decreased. The two children who were sensitized and developed clinical allergy to birch showed persistent IL-4 and IL-5 production and IL-9 mRNA expression, as well as Th2-associated IgG4 responses. Transient Th2-like responses were observed among the other children. Proliferative responses and IgG1 antibodies were seen in all children. Immune responses to birch can be demonstrated in all children, during the first 7 years of life, regardless of atopic status. A transient early Th2-like response is down-regulated after the fourth pollen season, except in children who develop clinical allergy to the particular allergen.

Immune response to respiratory syncytial virus in young Brazilian children.

We have evaluated the cellular and humoral immune response to primary respiratory syncytial virus (RSV) infection in young infants. Serum specimens from 65 patients <=12 months of age (39 males and 26 females, 28 cases <3 months and 37 cases > or = 3 months; median 3 3.9 months) were tested for anti-RSV IgG and IgG subclass antibodies by EIA. Flow cytometry was used to characterize cell surface markers expressed on peripheral blood mononuclear cells (PBMC) from 29 RSV-infected children. There was a low rate of seroconversion in children <3 months of age, whose acute-phase PBMC were mostly T lymphocytes (63.0 +/- 9.0%). In contrast, a higher rate of seroconversion was observed in children >3 months of age, with predominance of B lymphocytes (71.0 +/- 17.7%). Stimulation of PBMC with RSV (2 x 10(5) TCID50) for 48 h did not induce a detectable increase in intracellular cytokines and only a few showed a detectable increase in RSV-specific secreted cytokines. These data suggest that age is an important factor affecting the infants' ability to develop an immune response to RSV.

Antibody subclass profile and avidity during acute and chronic human Schistosoma mansoni infection

The avidity of IgA, IgM, IgG and IgG subclass antibodies against Schistosoma mansoni soluble egg antigen (SEA) was determined by ELISA in serum samples collected in 1995 from individuals in Brazil with acute ( n = 36) and chronic ( n = 40) schistosomiasis. Fifteen individuals at the acute phase were also evaluated 6 months after clinical diagnosis. Predominance of low-avidity IgG, IgG1, IgG2, IgG3 and IgA characterized the acute phase. IgG4 was detected in only 2 individuals with acute disease (5·6%). Levels of anti-SEA IgM were similar between the study groups. IgG1 avidity showed the strongest association with the chronological evolution of the infection, presenting 100% of low avidity during the acute infection and reaching 100% of high avidity 6 months after. It is suggested that distinct anti- Schistosoma egg antigens subclass profile and antibody avidity characterize the clinical phases of S. mansoni infection. In particular, determination of anti-SEA IgG1 offers a new tool for the laboratory analysis of the disease.

IgG antibody subclass responses determined by immunoblot in infants’ sera following vaccination with a meningococcal recombinant hexavalent PorA OMV vaccine

The introduction of meningococcal serogroup C conjugate vaccines into the UK immunisation schedule has led to the decline of serogroup C disease in those vaccinated but there is no imminent vaccine solution for serogroup B disease. The PorA outer membrane protein (OMP) is a potential serogroup B vaccine candidate and an outer membrane vesicle (OMV) vaccine containing six different PorA OMPs (each representing a different serosubtype) has been evaluated in phase II trials with encouraging results. Little is known about the IgG subclass response to the various antigens contained within this vaccine. These responses are important due to the different half-lives and complement fixing abilities of these antibodies. In this study, immunoblotting was undertaken with infants’ sera following either three or four doses of vaccine, and OMVs from six isogenic meningococcal strains differing only in their PorA serosubtype. Following either three or four doses of the vaccine, IgG 3 and IgG 1 subclass antibodies were induced to all six of the isogenic strains, although sera collected after four doses of vaccine showed stronger antibody levels. IgG 3 was found in more sera than IgG 1. For both sets of sera, the two isogenic strains expressing P1.5,2 and P1.5 c,10 induced stronger IgG subclass antibody responses than the other four meningococcal strains. The recombinant hexavalent PorA OMV vaccine stimulates both IgG 1 and IgG 3 subclass antibodies, the subclasses that are most effective in activating the complement system.

Purification and characterization of monoclonal antibodies against the free alpha-subunit of human chorionic gonadotrophin.

Monoclonal antibodies (Mabs) against human chorionic gonadotropin hormone (hCG) were raised by hybridoma technology using Sp2/0 myeloma cells as fusion partner. Sixty-five percent of the total culture wells exhibited hybrid growth and 8% of the total wells (13 culture wells) contained anti-hCG secreting hybrids. A positive hybrid cell line secreting antibodies against the free alpha-subunit of hCG was cloned twice by limiting dilution method and eighty four clones were obtained that secreted monoclonal antibodies anti-alpha hCG. One of these hybridoma clones (1C4) secreting monoclonal antibodies against the free alpha-subunit of hCG was selected for purification and characterization purposes. This hybridoma cell line secreted monoclonal antibodies of IgG1 subclass, which were purified by affinity chromatography on Protein A Sepharose CL-4B column with a final relative recovery of antibody activity of 75% and a purification factor of about 12. The purified preparation was analyzed by SDS-PAGE, native PAGE, and IEF. Specificity studies of this Mab revealed that it recognized specifically an epitope on the free alpha-subunits of hCG, FSH, LH, and TSH as determined by enzyme immunoassays. On the other hand, this Mab exhibited crossreactivity with other pituitary hormones either as free subunits or intact molecules as follows: alpha hCG 100%; intact hCG 1.8%; beta hCG 0.14%; alpha FSH 24.5%; intact FSH 0.8%; beta FSH 0.09%; alpha LH 20.5%; intact LH 0.9%; beta LH 0.08%; alpha TSH 50.5%; intact TSH 3.7%; beta TSH 0.07%; The affinity constant (K) of this Mab with respect to free alpha-subunit of hCG was found to be 1.5 x 10(7) I/mol as determined by the simple antibody dilution analysis method.

Serotype of Streptococcus pneumoniae capsular polysaccharide can modify the Th1/Th2 cytokine profile and IgG subclass response to pneumococal-CRM 197 conjugate vaccines in a murine model

The cellular and antibody responses to type 14 and type 19F Streptococcus pneumoniae capsular polysaccharides (PS) conjugated to CRM 197 were investigated in a mouse model developed for pre-clinical evaluation and quality control of pneumococcal conjugate vaccines. Total IgG antibody and IgG subclasses against PS and the carrier protein for both conjugates were measured in addition to the T cell proliferation and cytokine profiles induced by these conjugates. While unconjugated PS 14 and 19F were at best only weakly immunogenic, both types of conjugate induced strong primary and secondary IgG responses to PS. The responses induced by the two conjugates to the carrier protein were very different; a high level of anti-CRM 197 IgG was induced only by the PS19F conjugate whereas a very weak response was induced by the PS14 conjugate. Interestingly, the IgG subclass distribution was different for the two conjugates; for PS19F conjugate, the IgG response was almost completely of IgG1 subclass with low levels of IgG3 and IgG2a while the response to PS14 conjugate was mainly of the IgG1 and IgG2a subclasses with a low level of IgG3. The anti-CRM 197 IgG subclass distribution was identical with that to the corresponding conjugated PS. Both types of conjugate induced strong T cell proliferation to recall antigens but induced different patterns of cytokine response in immune spleen cells which were indicative of a Th0 response or a mixture of Th1 and Th2 responses with a bias towards Th2 response in PS19F-CRM 197 immunised mice. In conclusion, PS14- and PS19F-CRM 197 conjugates induced different IgG subclass patterns as a result of inducing different patterns of cytokine response to the carrier protein. This indicates that the serotype of PS can modify the Th1/Th2 response to the carrier protein, which has a direct effect and can predict the IgG subclass of the PS response. Finally, we conclude that this model appears suitable for studying the immunogenicity and immune interaction of different components of multivalent pneumococcal conjugate vaccines and may be applicable to their pre-clinical evaluation and quality control.

Myiasis Due to Hypoderma lineatum Infection Mimicking the Hypereosinophilic Syndrome

Myiasis Due to Hypoderma lineatum Infection Mimicking the Hypereosinophilic Syndrome

IgG-subclass antibody responses and the natural history of hepatic cystic echinococcosis in asymptomatic patients.

Given that cystic echinococcosis (CE) is a serious clinical problem in endemic countries, there is still relatively little information available on the natural history of the human disease. The aim of the present study was to correlate serological status with pathology, in ultrasound-characterised, asymptomatic cases of human CE. Serum concentrations of IgG reacting with antigen B from cyst fluid and of similarly specific IgG1, IgG2, IgG3 and IgG4 were determined by ELISA and further investigated by immunoblotting. CE cases with simple cysts (Type I), or cysts with clear laminations and daughter cysts (Types II and III) exhibited elevated IgG4 seropositivity, whereas concentrations of specific IgG1 and IgG4 declined in CE cases characterised by cyst infiltration or calcifications (Types IV and V). The responses of each specific IgG subclass were used, in association with an ultrasound classification, to try to develop an immunoserological natural-history profile of CE in asymptomatic patients. Specific IgG4 antibody responses were particularly associated with the evolutive phase of CE (Types I, II and III), whereas the IgG1, IgG2 and IgG3 responses tended to be associated with the involutive phase (Types IV and V). These results indicated that an IgG4 antibody response was associated with (or was a marker for) cystic development, growth and disease progression, whereas the IgG1, IgG2 and IgG3 responses occurred predominantly when cysts became infiltrated or were destroyed by the host. The findings support the view that evolutive and subsequent involutive phases occur in untreated CE.

Skin prick test and serological analysis with recombinant group 2 allergens of the dust mites L. destructor and T. putrescentiae.

The dust mites Lepidoglyphus destructor and Tyrophagus putrescentiae are important sources of allergen in farming environments. The major allergens of the dust mites L. destructor and T. putrescentiae have been cloned and expressed as recombinant proteins. To evaluate the use of recombinant group 2 allergens of L. destructor (rLep d 2) and T. putrescentiae (rTyr p 2) in skin prick test (SPT), and serological analysis in sensitized and non-sensitized farmers chronically exposed to dust mites. Skin prick test with rLep d 2, rTyr p 2 and the corresponding commercial extracts was performed in 44 farmers sensitized to L. destructor and/or T. putrescentiae, and 38 control farmers. IgE and IgG subclass antibodies to the recombinant allergens were analysed by RAST and ELISA, respectively. Out of the 44 subjects positive in SPT to L. destructor and/or T. putrescentiae extract, 26 (59%) displayed a positive SPT to one or the other of the recombinant allergens, whereas 21 (48%) were positive to both. Significant correlations were registered between the sizes of the weals induced by rLep d 2 and rTyr p 2 and the corresponding RAST values (P < 0.001). A majority of subjects positive in SPT to the recombinant allergens had detectable IgG4 antibodies, and the levels were significantly higher in the dust mite sensitized group than in the controls (P < 0.05). No such differences were found in the IgG1 values (P > 0.05). The results obtained with rLep d 2 and rTyr p 2 correlated relatively well with each other with respect to SPT, RAST and IgG4, suggesting that the allergens have similar or shared IgE epitopes. All the control subjects had a negative SPT and RAST to rLep d 2 and rTyr p 2. Recombinant group 2 allergens from the dust mite L. destructor and T. putrescentiae represent useful tools for diagnosis of dust mite allergy.

SERUM ANTIBODI-IMUNOGLOBULIN-G-SUBKLAS SPESIFIK TERHADAP NON-LEUKOTOKSIK ACTINOBACILLUS ACTINOMYCETEMCOMITANS

Serum specific IgG subclass antibodies to non-leukotoxic strains of Actinobacillus actinomycetemcomitans (Aa) NCTC 9710 and NCTC 10979 were quantified by radioimmunoassay. Samples were taken from sera of 10 patients with Juvenile Periodontitis (JP) and 10 from healthy periodontal individuals as control. The results show that JP patients had higher IgG 2 antibody levels to Aa NCTC 9710 (ABT 50 = 620) than the other IgG subclasses (IgG 1 = 300, IgG 3 = 370, and IgG 4 = 500). The JP patients had also higher IgG 2 antibody levels to Aa. NCTC 10979 (600) when compared with the other IgG subclasses (IgG 1 = 300, IgG 3 = 500, and IgG 4 = 400). Whilst, the control gorup had lower IgG subclass antibody level as compared with the JP group. In conclusion, the JP patients had an elevation of IgG 2 subclass antibodies to non-leukotoxic Actinobacillus actinomycetemcomitans.

Specific IgG subclass antibody pattern toAspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)

BACKGROUNDIgG and IgG subclass antibodies to Aspergillus fumigatus (A fumigatus) were measured in a large population of patients with cystic fibrosis to elucidate a putative antibody pattern specific for allergic...

Anti-Beta 2-Glycoprotein I Antibody Isotype and IgG Subclass in Antiphospholipid Syndrome Patients

Beta 2-glycoprotein I (β2-GPI) is an antigenic target recognised by antiphospholipid antibodies found in association with the antiphospholipid syndrome (APS). In this study, the prevalence of Immunoglobulin M (IgM) and IgA anti-β2-GPI antibodies was examined in APS patients and compared with IgG antibodies. In addition the value of measuring antibody isotypes and IgG subclass was investigated in the laboratory diagnosis of APS. A solid phase enzyme linked immunosorbent assay was established to measure IgG, IgM and IgA and IgG subclass antibodies to β2-GPI in patients with APS and a variety of other thrombotic and non-thrombotic disorders. Raised levels of IgM anti-β2-GPI antibodies were observed in 65% of patients with APS, 21% with systemic lupus erythematosus (SLE), 23% with rheumatoid factor, 4% with stroke, 5% carotid artery stenosis (CAS), 17% with a biological false positive serology for syphilis, 43% with infectious mononucleosis (IM) and 27% with human immunodeficiency virus (HIV). The median value for IgM antibodies to β2-GPI for all these groups ranged from 2 to 7 arbitrary units (AU). Elevated levels of IgA antibodies to β2-GPI were found in patients with APS (47%), SLE (13%), rheumatoid factor (26%), CAS (48%), stroke (25%), VDRL false positive serology for syphilis (33%), IM (47%) and HIV (7%). The median value of IgA antibodies to β2-GPI in all of these groups ranged from 2 to 4 AU. Conversely the median value for IgG anti-β2-GPI in APS patients was 112 AU compared to 1-4 AU in the other conditions examined. The presence of IgM and IgA antibodies to β2-GPI was much less specific and sensitive for APS than IgG, with raised levels of these isotypes seen in a variety of thrombotic and non-thrombotic disorders. Elevated levels of IgG1, IgG2, IgG3 and IgG4 antibodies to β2-GPI were detected in APS patients. While all four IgG anti-β2-GPI antibody subclasses were represented in APS patients there appeared to be a significant overall skewing towards to the lgG2 subclass.

IgG subclass of antibodies to Yo in patients with paraneoplastic cerebellar degeneration

IgG subclass of antibodies to Yo in patients with paraneoplastic cerebellar degeneration

Comparison of IHA test for diagnosis of hydatid cyst in human, with use from birds RBC.

A major problem in the serodiagnosis of human toxocariasis in tropical countries is cross-reaction with antibodies to other helminthic diseases and a lack of sensitivity. The majority of tests currently available use total IgG and, in this study, the use of peroxidase-conjugated anti-human IgG subclass antibodies (IgG1-4) was compared with total IgG for the diagnosis of human toxocariasis by using Toxocara excretory–secretory (TES) antigens in an enzyme-linked immunosorbent assay (ELISA) format. All four IgG subclass antibodies gave approximately 10-fold increases in optical density (OD) values for 50 toxocariasis patients compared to 29 healthy normals; this was significantly greater than the approximate doubling of OD values seen in the total IgG-ELISA format. IgG2 gave by far the greatest sensitivity (values: IgG, 50%; IgG1, 60%; IgG2, 98%; IgG3, 78%; IgG4, 64%). Significant cross-reactivity using all IgG subclasses in the TES ELISA was seen with 141 serum samples from patients with 10 other helminthic infections. However, IgG3 gave the best specificity (values: IgG, 73%; IgG1, 76%; IgG2, 71%; IgG3, 81%; IgG4, 71%). Thus, of the IgG subclass antibodies, IgG2 appeared best and employing this subclass can improve the serodiagnosis of human toxocariasis since it recognises carbohydrate epitopes of TES antigens.

IgG subclass antibodies to glutamic acid decarboxylase and risk for progression to clinical insulin-dependent diabetes

Pancreatic islet beta cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is believed to be mediated by a T-helper 1 (T H1) lymphocyte response to islet antigens. In the mouse, T H1 (IL-2, IFN-γ) and T H2 (IL-4, -5, -6, -10) responses are associated with the generation of IgG2a and IgG1 subclasses, respectively. The equivalent human subclasses have not been defined. Because the IgG subclass response to an antigen may be a potentially useful marker of T H1/T H2 immune balance we measured IgG subclass antibodies to glutamic acid decarboxylase (GAD), a major islet autoantigen in IDDM, in 34 newly-diagnosed IDDM patients and in 28 at-risk, first-degree relatives of people with IDDM. In the newly-diagnosed patients, total IgG antibodies to GAD were detected in 74% (25/34); IgG1 and/or IgG3 were significantly more frequent than IgG4 or IgG4/IgG2 (14/34 versus 5/34, p = 0.01). GAD antibody-negative patients were significantly younger ( p = 0.01). In 15 at-risk relatives who had not progressed to clinical diabetes after a median of 4.5 years, 10 had IgG2 and/or IgG4 antibodies compared to only 3/13 progressors ( p = 0.02). Total IgG and IgG2 antibodies were higher in non-progressors. Non-progressors were older than progressors ( p = 0.01), and relatives with IgG2 and/or IgG4 responses were also older ( p = 0.01). These results suggest that IgG subclass antibodies to GAD may contribute to diabetes risk assessment in islet antibody relatives.

IgG Antibodies in Leprosy and Their Relation to Thl/Th2 Responses

The study of the IgG subclasses of antibodies across the clinical spectrum of leprosy id not reveal differences that could be related to the Th1/Th2 dichotomy; the predominance of antibodies of the IgG1, 2 and 3 subclasses suggest a possible Th1 response across the spectrum in Venezuelan patients. In contrast, the anergic form of American cutaneous leishmaniasis was characterized by a strong IgG4 specific antibody response, suggesting a Th2 response, while localized forms of the disease appeared to be associated with responses of the Th1 type. Persisting antibodies to phenolic glyco- lipid-I in a small percentage of clinically inactive multibacillary patients may reflect differences in the catabolism of this unusual antigen, since persistence was not associated with a unique initial IgG subclass response to a complex extract of Mycobacterium leprae antigens.

The Role of IgG1 and IgG2 in Trimellitic Anhydride-Induced Allergic Response in the Guinea Pig Lung

Trimellitic anhydride (TMA) is a small molecular weight chemical used in the paint and plastics industry that can cause asthma-like symptoms in humans. Guinea pigs sensitized intradermally with TMA will respond to antigen challenge with asthma-like symptoms, including an immediate bronchoconstriction and a delayed cellular infiltration into the lung, particularly eosinophil infiltration. Sensitized guinea pigs produce TMA-specific IgG1, which is thought to be important in asthmatic reactions in this animal model; however, they also produce TMA-specific IgG2 antibody. The purpose of the present study was to determine the role of IgG1 and IgG2 in the TMA-induced immediate bronchoconstriction and delayed cellular infiltration in the guinea pig. Guinea pigs were passively sensitized by intratracheal instillation of TMA-specific IgG2, an antibody preparation enriched with TMA-specific IgG1, or a combination of the two. The allergic response was induced by intratracheal instillation of TMA conjugated to guinea pig serum albumin (TMA–GPSA). A significantly greater bronchoconstrictor response was observed in animals sensitized with a combination of the IgG2 and IgG1 preparation compared to those sensitized with IgG2 or the IgG1 preparation alone. Cellular infiltration was quantified 24 h after antigen challenge by differential cell counts of bronchoalveolar lavage (BAL) cells as well as by using eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity as a measure of the numbers of eosinophils and neutrophils, respectively. In the BAL, passively sensitizing with IgG2 alone resulted in an increase in both TMA-induced MPO and EPO activity. In contrast, in the lung, passively sensitizing with a partially purified preparation of TMA-specific IgG1 alone resulted in a significant increase in TMA-induced EPO activity. Passively sensitizing with IgG2 in conjunction with the IgG1 preparation resulted in an enhanced cellular infiltration and lung injury over that seen with either antibody preparation alone. These data demonstrate an augmentation of IgG1-mediated responses by the addition of IgG2 and suggest a significant role for both subclasses of IgG antibodies in this guinea pig model of TMA-induced occupational asthma.

IgG Antibody Subclasses, Tumor Necrosis Factor and IFN-γ Levels in Patients with Type II Lepra Reaction on Thalidomide Treatment

A group of 9 Mexican lepromatous leprosy patients was studied at the beginning of a type II reaction (erythema nodosum leprosum, ENL) and after 1 or 2 months of thalidomide treatment. ENL patients at the onset of the reaction had slightly higher amounts of anti-Mycobacterium leprae IgG1 and IgG2 antibodies, compared to similar lepromatous patients that did not develop ENL. Neither these antibody levels nor IgM and the other IgG subclasses were importantly modified after thalidomide treatment. Serum TNF was significantly higher in the patients that developed ENL compared to those that did not develop the reaction. TNF levels were slightly decreased after 1 month of thalidomide treatment and significantly decreased after 2 months of treatment. Serum IFN-γ was significantly lower in patients at the onset of ENL and was increased after 1 and 2 months of thalidomide treatment.

Seasonal variation of IgG subclass antibodies to house dust mite in sera from mite-sensitive asthmatic patients.

House dust mite is an important cause of bronchial asthma. Seasonal variation of environmental house dust mite allergen levels and the specific IgE antibody to house dust mite have been reported. We studied the changes in IgG subclass antibodies to house dust mite associated with seasonal variation of house dust mite allergen levels in houses of mite-sensitive asthmatic patients. In 14 mite-sensitive asthmatic patients, house dust mite allergen (Der f 1) contents in bedding were measured monthly, and IgG subclass antibodies to house dust mite, Dermatophagoides farinae (D. farinae), were determined by enzyme-linked immunosorbent assay (ELISA) every 3 months from July to December. The concentration of Der f 1 in dust from bedding reached maximum levels in August and September, and significantly decreased in November and December compared with August and September (P < .05). Levels of D. farinae-specific IgG4 antibodies significantly decreased in December compared with September (P < .05) with no statistically significant change between September and June (P > .05). Levels of D. farinae-specific IgG2 antibodies decreased significantly in December compared with June (P < .05). The levels of IgG1 and IgG3 antibodies to D. farinae showed no significant differences during the study period. These findings suggest that seasonal changes in natural exposure to house dust mite allergen might lead to concurrent changes in specific IgG4 antibodies to house dust mite in mite-sensitive asthmatic patients and each IgG subclass antibodies to house dust mite might have a different kinetics.

IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria.

In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.