Immune response to the 7-valent pneumococcal conjugate vaccine in 30 asplenic children

The aim of the study was to determine the concentration of pneumococcal antibodies after a dose of 7-valent pneumococcal conjugate vaccine (PCV7) in 30 asplenic children between 4 months and 19 years of age. Fifteen children had received pneumococcal polysaccharide vaccine (PPV) approximately 5 years prior to vaccination with PCV7. The antibody concentrations against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were measured by ELISA before and after the PCV7 vaccination. Before vaccination with PCV7, the antibody concentrations were similar in children who had or had not received PPV previously. A dose of PCV7 stimulated a good immune response in asplenic patients. Prior immunization with PPV did not affect the antibody concentration after the vaccination with PCV7. In conclusion, asplenic children vaccinated with PPV may need revaccination with PPV earlier than the recommended 3–5 years after the first dose. PCV7 induces a satisfactory immune response in asplenic patients and should be considered as an alternative vaccine in that patient group.     

Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasible. We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second dose. The spleen remains necessary for a fast, primary response to (blood-borne) polysaccharides, even when they are presented in a conjugated form. Coadministration of a conjugate vaccine with additional nonconjugated polysaccharides of other serotypes did not improve the response to the nonconjugated polysaccharides. We conclude that pneumococcal conjugate vaccines can be of value in protecting asplenic or hyposplenic patients against pneumococcal infections.     

Humoral responses to oxidized low-density lipoprotein and related bacterial antigens after pneumococcal vaccine

Antibodies to oxidized low-density lipoprotein (oxLDL) may modulate the development of atherosclerosis. Antibodies to oxLDL may also react with cell wall polysaccharides (CWPS) of Streptococcus pneumoniae because both antigens share a common phosphorylcholine moiety. In hypercholesteremic mice, immunization with pneumococcal organisms elicited antibodies to oxLDL and protection against atherosclerosis. In humans, we determined whether the widely used adult pneumococcal polysaccharide vaccine augmented antibodies to oxLDL, CWPS, and phosphorylcholine, providing the potential to retard atherogenesis. Before and 4 weeks after pneumococcal vaccination of 23 healthy adults (11 smokers and 12 matched nonsmokers), we characterized IgG, IgM, and IgA to pneumococcal capsular polysaccharides, CWPS, and phosphorylcholine, IgG and IgM to oxLDL, and fasting serum lipids. The pneumococcal vaccine elicited significant increases in each antibody class to surface capsular polysaccharides. In contrast, only IgG to CWPS increased modestly and only among smokers. Moreover, antibodies to neither phosphorylcholine nor oxLDL increased consistently in either group. The pneumococcal polysaccharide vaccine effectively elicits antibodies to the bacterial capsule. The vaccine had no effect on serum lipids. The vaccine did not augment antibodies to CWPS, to its component phosphorylcholine, or to oxLDL, which are antibodies that have been proposed to modify the uptake of oxLDL by macrophages and the pathogenesis of atherosclerosis.     

Immunization of female mice with glycoconjugates protects their offspring against encapsulated bacteria

The immune system of the newborn is immature, and therefore it is difficult to induce protective immunity by vaccination in the neonatal period. Immunization of mothers during pregnancy against infections caused by encapsulated bacteria could thus be particularly attractive, as infants do not respond to polysaccharide (PS) antigens. Transmission of maternal vaccine-specific antibodies and protection of offspring against pneumococcal bacteremia and/or lung infection were studied in a neonatal murine model of pneumococcal immunization and infections. Adult female mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were measured in sera of mothers and their offspring. Effective transmission of maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3-week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a significant correlation between maternal and offspring antibody levels was observed. The PPS-specific antibodies persisted for several weeks but slowly decreased over time. Offspring of Pnc-TT-immunized mothers were protected against pneumococcal infections with homologous serotypes, whereas PPS immunization of mothers did not protect their offspring, in agreement with the low titer of maternal PPS specific antibodies. When adult female mice were immunized with a meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and transmission were similar to those observed for pneumococcal antibodies. Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM-immunized mothers. These results demonstrate that this murine model of pneumococcal immunization and infections is suitable to study maternal immunization strategies for protection of offspring against encapsulated bacteria.     

Antibody Response to a Seven-Valent Pneumococcal Conjugated Vaccine in Patients with Ataxia-Telangiectasia

Immunodeficiency is a characteristic feature of ataxia-telangiectasia (A-T). Humoral immunodeficiency generally consists of hypogammaglobulinemia and impaired antibody response to bacterial and viral antigens. We previously observed defective antibody response to 23-valent pneumococcal polysaccharide vaccine (PPV) in 96% of 29 patients with A-T. In this study, we investigated the antibody response to a seven-valent pneumococcal conjugate vaccine, PCV7, in 14 patients with A-T. IgG antibody levels to four pneumococcal serotypes, 6B, 14, 19F, 23F, which were included in PCV7, were measured by ELISA in pre- and postimmunization serum samples. Antibody titers against each individual Streptococcus pneumoniae serotype was considered to be positive when serotype specific pneumococcal antibody titer was higher than 10% (>10 U/mL) of the reference plasma pool level. However, when the fold increase (FI) in postimmunization antibody titer was less than two, the subject was determined to be unresponsive to the given serotype. The values were compared with the results obtained in age- and ethnic-matched children after one dose of PPV. Only two patients produced antibodies to one serotype each; one to serotype 19 with a fold increase of <2, and the other to serotype 23F with a fold increase of 5.7 based on the above criteria, although the differences between pre- and postvaccine antibody titers for serotypes 14, 19, and 23 appeared to be statistically significant. In conclusion, A-T patients failed to respond to one dose of PCV7 vaccine. Two or more doses of conjugated vaccine may be required to recruit the help of T lymphocytes in A-T patients.     

Immunogenicity and tolerance of a 7-valent pneumococcal conjugate vaccine in nonresponders to the 23-valent pneumococcal vaccine

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 microgram/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 microgram/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.     

IgG Subclass Antibody Responses to Pneumococcal Polysaccharide Vaccine in Splenectomized, Otherwise Normal, Individuals

Subclasses of IgG antibodies to pneumococcal polysaccharide serotype antigens 4, 6A, and 23F were measured before and 4 weeks after vaccination with pneumococcal vaccine in young individuals splenectomized because of trauma and in a control group. An ELISA technique was applied. IgG2 anti-pneumococcal antibodies predominated before vaccination, especially against serotypes 4 and 6A. The youngest individuals in the splenectomy group tended to have lower IgG2 anti-pneumococcal antibody levels than the older ones. Vaccination induced antibodies of the IgG1 and IgG2 subclasses, and in some individuals also of the IgG4 subclass. Splenectomy does not seem to influence the IgG subclass pattern of antipneumococcal antibodies.     

Class and subclass anti-pneumococcal antibody responses in splenectomized patients

Antibody titres against pneumococcal capsular and cell wall antigens and the immune response to polyvalent pneumococcal vaccine were measured in 21 splenectomized patients and 12 healthy controls. Most individuals possessed anti-pneumococcal capsular polysaccharide antibodies of IgG, IgA and IgM classes. The anti-capsular IgG was predominantly of the IgG1 and IgG2 subclasses; only occasional individuals had any detectable titre in IgG3 or IgG4 subclass. Most individuals responded to immunization with Pneumovax. There was no clear difference between groups of control and splenectomized subjects, although three of the splenectomized patients had undetectable pre-immunization anti-capsular titres in one or more subclass which failed to rise following immunization. All subjects tested had anti-phosphocholine antibodies in IgG, IgA and IgM classes with the exception of a single splenectomized patient who lacked detectable anti-phosphocholine IgM. Pre-immunization titres where similar in healthy controls and splenectomized patients. There was no demonstrable rise in anti-phosphocholine titre following immunization with Pneumovax.     

Maternal immunity and antibody response of neonatal mice to pneumococcal type 19F polysaccharide.

The effect of immunization of mothers on the antibody response of their young to pneumococcal type 19F polysaccharide was studied. When 2-week-old BALB/c mice from mothers immunized with 23-valent pneumococcal vaccine during gestation were given an additional dose of the same vaccine, mouse pneumococcal antiserum, or both, they produced higher titers of antibodies to the 19F polysaccharide (1.87 to 4.66 micrograms of 19F immunoglobulin M [IgM] antibody per ml of serum; 0.45 to 0.81 micrograms of IgG antibody per ml of serum) than the control group that did not receive any treatment after birth (0.69 micrograms of 19F IgM antibody per ml; 0.28 micrograms of 19F IgG antibody per ml) (P less than 0.01). Furthermore, all 11- to 12-week-old monkeys that received an additional dose of 23-valent vaccine, pneumococcal immunoglobulin, or both produced statistically higher titers of IgG antibody to the 19F polysaccharide than did controls at various ages. The titers (micrograms of IgG antibody per milliliter of serum) were as follows: vaccine group, 7.12 +/- 0.96; control group at 4 months of age, 3.82 +/- 0.74 (P less than 0.01); immunoglobulin-treated group, 6.85 +/- 0.76; vaccinated and immunoglobulin-treated group, 7.80 +/- 1.40; control group at 3 months of age, 3.01 +/- 0.61 (P less than 0.01). These results suggest that immunization of mothers under certain conditions, such as with an optimum dose of antigen at a critical period of gestation or postnatal development, could provide young infants with an enhanced antibody response to pneumococcal polysaccharide immunogens.     

Determination of Antibody Responses of Elderly Adults to All 23 Capsular Polysaccharides after Pneumococcal Vaccination

The 23-valent pneumococcal polysaccharide vaccine was formulated to prevent invasive infection in the elderly and other high-risk populations from the most prevalent Streptococcus pneumoniae serotypes. However, the immunogenicity of all 23 vaccine polysaccharides has not been fully characterized in elderly adults. We previously reported that whereas the majority of elderly subjects had vigorous immune responses to selected pneumococcal vaccine polysaccharides, a subset of elderly individuals responded to fewer than two of seven vaccine serotypes after immunization. To determine whether these elderly low responders have a general inability to respond to pneumococcal vaccine and to determine whether elderly low responders might be identified by their responses to a few polysaccharides, we measured antibody responses of elderly adults to all 23 vaccine polysaccharides after pneumococcal immunization. As a group, elderly subjects showed a significant rise after immunization in geometric mean antibody levels to all 23 vaccine serotypes. However, when individual rather than group immune responses were assessed, the 23-valent vaccine did not appear to be uniformly immunogenic in these elderly subjects. Eleven elderly subjects (20%) had twofold increases in specific antibody after vaccination to only 5 or fewer of the 23 vaccine polysaccharides, and they did not respond to the most prevalent serotypes causing invasive disease. Antibody responses to serotype 9N were found to reliably distinguish low vaccine responders from other elderly subjects. However, no particular group of vaccine polysaccharides could be used as a marker for adequate immune responses if only postvaccination sera were analyzed.     

Pneumococcal vaccination in splenectomized patients with hematological disorders

Seventy splenectomized patients were vaccinated with Pneumovax, a pneumococcal polysaccharide vaccine. Twenty-four of the patients had a malignant and 30 a nonmalignant hematological disorder. The remaining 16 were patients with no known hematological disorder, seven with intra-abdominal carcinomas and nine with non-malignant reasons for splenectomy. About 90% of the patients with non-malignant hematological disorders responded to vaccination with a rise in antibody titres, which was significantly higher than in the other two groups studied. Malignant hematological disorders lowered the response rate to 61-67%. Patients with no known hematological disorder but with intra-abdominal carcinomas also responded less frequently, while those in this group with other surgical reasons for splenectomy had a response rate comparable to healthy individuals. No serious side-effects were reported and we therefore conclude that all splenectomized patients should be vaccinated with a pneumococcal vaccine. However, it must always be born in mind that one third of the patients with malignant disease did not respond to vaccination.     

The effect of T cell independent and cross-reactive antigen on the immune response to pneumococcal conjugate vaccination

The effect of priming with various antigens on subsequent vaccination with the pneumococcal conjugate vaccine (CPV) was determined using BALB/c mice. Priming with pneumococcal polysaccharide or cross-reactive polysaccharide did not inhibit the IgG response to CPV immunization. Additionally, live intranasal colonization by Streptococcus pneumoniae or cross-reactive organism resulted in higher IgG responses to CPV. These results suggest that colonization elicits immunological memory capable of boosting the immune response to CPV.     

Immunogenicity of 23-valent pneumococcal polysaccharide vaccine in children with human immunodeficiency virus undergoing highly active antiretroviral therapy.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (23PSV) has been recommended for children infected with human immunodeficiency virus (HIV); however, the efficacy of this vaccination in HIV-infected children undergoing highly active antiretroviral therapy (HAART) has not been studied. OBJECTIVE: To study the immunogenicity and immunologic protection of 23PSV in HIV-infected children after stable HAART. METHODS: Serotype-specific IgG antibodies to 12 pneumococcal capsular polysaccharides were analyzed before and after 23PSV vaccination in 41 HIV-infected children undergoing HAART and compared with 95 HIV-negative control children. Seropositivity, clinical protection, and additional clinical protection from 23PSV were calculated based on serotype specific IgG antibody levels and on the known incidence of these serotypes for causing invasive disease. RESULTS: Children with HIV infection undergoing HAART developed a significant increase in specific IgG levels to Streptococcus pneumoniae after 23PSV vaccination (0.95 vs 1.84 micro/gmL, P < .001). The HIV-infected children with CD4+ cell counts of 25% or higher at the time of vaccination developed a higher additional clinical protection gain from 23PSV vaccination than did children with a lower percentage of CD4+ cells. CONCLUSIONS: HIV-infected children undergoing stable HAART develop a significant immunologic response to 23PSV, especially those with higher T-cell counts and lower viral loads at the time of vaccination.     

Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation.

Immunoglobulin class- and subclass-specific antibodies to a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II) were measured before and after immunization in children, 1 year or more after bone marrow transplantation for a variety of genetic disorders. The median titres of specific IgG, IgG1 and IgG2 pneumococcal antibodies fell significantly (P less than 0.05) from pre-transplantation levels. The levels of pneumococcal antibodies in the patients before immunization were markedly lower than those in control children of comparable age, for antibodies of IgM, IgG, IgG1 and IgG2 classes (P = less than 0.001 in each case). Apart from IgG2 antibodies, the median response to immunization with Pneumovax II was not significantly different from the controls (P greater than 0.05). However, because of the lower pre-immunization levels, the patients did not achieve a high post-immunization-specific antibody titre in any immunoglobulin class or subclass, when compared with normal children. Neither the pre-immunization specific antibody levels nor the response to immunization were affected by splenectomy or the presence of chronic graft-versus-host disease. Immunization of the donor before bone marrow harvest did not influence the level of specific antibody 1 year or more after transplantation. No significant correlation was found between the total serum IgG2, the patients' age at the time of assessment, or time after transplantation, and the IgG2-specific antibody response. The lack of specific antibodies and the poor IgG2 response to pneumococcal antigens may contribute towards the occurrence of infection with Streptococcus pneumoniae in the late post-transplantation period.     

Evaluation of antibody responses to pneumococcal vaccines with ELISA and opsonophagocytic assay

Antibodies to a capsular polysaccharide (PS) provide protection against Streptococcus pneumoniae which express the homologous capsular serotype, and pneumococcal vaccines are designed to induce antibodies in the capsular PS. Levels and opsonophagocytic capacity of antibodies to the capsular PS of S. pneumoniae serotype 19F were determined by sera from adults immunized with 23-valent S. pneumoniae capsular PS vaccines. Geometric means of IgG anti-19F antibody level and specific opsonic titer rise significantly after immunization. The level of anticapsular PS antibodies for S. pneumoniae 19F serotype is fairly well correlated (r2=O.63) with the opsonophagocytic activities of sera. However, 3.7% (1/27) of serum samples display strikingly less opsonophagocytic activity than expected on the basis of their antibody level. Thus, antibody level may be of general use in predicting vaccine-induced protection among adults for 19F serotype. However, the opsonic activity data suggest that antibody levels are not always indicative of functional antibody.     

Pneumococcal sepsis and meningitis in vaccinated subjects: a review of 55 reported cases

Fifty-five cases of the occurrence of serious pneumococcal infections in both splenectomized and nonsplenectomized individuals who received pneumococcal vaccine were reviewed from the literature. Reasons for vaccine failure included the occurrence of non-vaccine-type pneumococcal infections (18 cases), possible poor antibody response to the vaccine, especially if it is given postsplenectomy and/or following intensive steroid or other immunosuppressive therapy, and decline in antibody titer over time. Although the total number of vaccinated individuals is unknown, the overwhelming majority of the many thousands of vaccinees have been successfully protected with pneumococcal vaccine. In spite of very rare vaccine failures, pneumococcal vaccination (and perhaps penicillin prophylaxis) is strongly recommended for patients at high risk of developing serious pneumococcal infections, including all individuals undergoing splenectomy for any reason, or for those who have had a splenectomy or have functional asplenia.     

Antibody Response to a T-Cell-Independent Antigen Is Preserved after Splenic Artery Embolization for Trauma

Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function assessed by examining the antibody response to polysaccharide antigens (pneumococcal 23-valent polysaccharide vaccine), B-cell subsets, and the presence of Howell-Jolly bodies (HJB). The data were compared to those obtained from splenectomized patients and healthy controls (HC) who had been included in a previously conducted study. A total of 30 patients were studied: 5 who had proximal SAE, 7 who had distal SAE, 8 who had a splenectomy, and 10 HC. The median vaccine-specific antibody response of the SAE patients (fold increase, 3.97) did not differ significantly from that of the HC (5.29; P = 0.90); however, the median response of the splenectomized patients (2.30) did differ (P = 0.003). In 2 of the proximally embolized patients and none of the distally embolized patients, the ratio of the IgG antibody level postvaccination compared to that prevaccination was <2. There were no significant differences in the absolute numbers of lymphocytes or B-cell subsets between the SAE patients and the HC. HJB were not observed in the SAE patients. The splenic immune function of embolized patients was preserved, and therefore routine vaccination appears not to be indicated. Although the median antibody responses did not differ between the patients who underwent proximal SAE and those who underwent distal SAE, 2 of the 5 proximally embolized patients had insufficient responses to vaccination, whereas none of the distally embolized patients exhibited an insufficient response. Further research should be done to confirm this finding.     

Response to pneumococcal vaccination in mannose‐binding lectin‐deficient adults with recurrent respiratory tract infections

Mannose‐binding lectin (MBL)‐deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL‐deficient patients with recurrent respiratory tract infections (RRTI). The response to pneumococcal vaccination in MBL‐deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL‐deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL‐deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL‐deficient and ‐sufficient patients with RRTI. Eighteen MBL‐deficient and 63 MBL‐sufficient adult patients with RRTI were all vaccinated with the 23‐valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL‐sufficient and ‐deficient patients. Forty‐three MBL‐sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL‐deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL‐sufficient and ‐deficient patients. In conclusion, our study suggests that MBL‐deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL‐sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL‐deficient patients with RRTI.     

The Antibody Response to Secondary Immunization with Pneumococcal Polysaccharides in Mice

The benefit of re-immunization with pneumococcal polysaccharide vaccine is an important question in clinical practice. In an experimental model, BALB/c and CBA/J mice were re-immunized s. c. with a 23-valent pneumococcal polysaccharide vaccine at various time intervals after a first immunization with the same vaccine. The antibody response after the secondary immunization showed similar kinetics as after primary immunization, and was mainly an IgM antibody response. Re-immunization at 28 days or earlier induced a decrease in the serum antibody levels to the vaccine. Reimmunization at 120 days or later induced higher antibody levels than after the first immunization. Significant increases in antibody levels to serotypes 1, 4, 7F and 19F out of six serotypes tested were observed. In CBA/J mice, but not in BALB/c mice, the dose used for primary immunization appeared to influence the magnitude of the antibody response to secondary immunization. Our results indicate that the time interval between primary and secondary immunization is an important determinant with regard to the magnitude of the antibody response to re-immunization with pneumococcal polysaccharide vaccine.     

Lack of effect of splenic regrowth on the reduced antibody responses to pneumococcal polysaccharides in splenectomized patients.

The experiments were to determine if ectopic splenic tissue in humans would restore to normal those antibody responses which are reduced in patients who have been splenectomized. The IgM and IgG antibody response to subcutaneous injection of polyvalent pneumococcal polysaccharide vaccine (PNEUMOVAX) was determined in 34 patients who had been splenectomized for trauma and 14 controls, by measuring the concentration of antibody specific for five of the serotypes in the vaccine in serum samples taken before and 1 month after the immunization. The patients had significantly lower post-immunization concentrations of IgM antibody for three of the five serotypes measured, and IgG for two of the five. The antibody response to the immunization was assessed by comparing the post- to the pre-immunization concentration of antibody by analysis of covariance. The patients had a significantly lower IgM response to three of the five serotypes measured and IgG response to four of the five. It is concluded that in adult humans the spleen is important in the maintenance of normal humoral immune responses. The presence and degree of ectopic splenic regrowth (splenosis) in the splenectomized patients was assessed by a spleen-specific radio-isotopic scan. There was no difference between patients with splenosis and those without, or between those with different degrees of splenosis, in any of the parameters of the antibody response measured. This is in vivo evidence indicating that ectopic splenic tissue in humans does not normalize the altered antibody responses observed following splenectomy.