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Biomedical subjects

J M Griffiss

Publications and source records attributed to J M Griffiss.

At least 37 records · Page 2Linked to original sources
PubMed1993

HLA expression by benign and malignant prostatic epithelium: augmentation by interferon-gamma.

Chronic prostatitis is a poorly understood entity that is characterized by lymphocytic infiltration of benign prostatic epithelium. Previously, we and others have shown that prostatic epithelium involved by prostatitis is phenotypically different from uninvolved epithelium. In addition, we have shown that malignant prostatic epithelium is rarely, if ever, infiltrated by lymphocytes. We now report that benign prostatic epithelium expresses HLA-DR only in the presence of lymphocytic inflammation, and that benign epithelium without chronic prostatitis and malignant prostatic epithelium do not express HLA-DR. In order to determine whether HLA-DR expression is inducible on malignant prostatic epithelium and therefore, at least theoretically, susceptible to immune regulation, we studied the DU-145 cell line in culture under various conditions. DU-145 cells did not express HLA-DR under routine culture conditions. However, the addition of interferon-gamma (100 to 6000 U/ml.) resulted in HLA-DR expression by DU-145 cells at 24 hours with maximal expression by 72 hours. In contrast, other cytokines (tumor necrosis factor, interleukin-1, interleukin-2) had no effect on HLA-DR expression. These investigations show that interferon-gamma induces HLA-DR expression on the DU-145 prostatic adenocarcinoma cell line, raising the theoretical possibility that malignant prostatic cells may be induced in vivo to express HLA-DR and thus become susceptible to immune regulation.

Adenocarcinoma↗
PubMed1993

The immune response of children to meningococcal lipooligosaccharides during disseminated disease is directed primarily against two monoclonal antibody-defined epitopes.

A human inhibition monoclonal ELISA (HIMELISA) was used to investigate the immune response of infants and children to meningococcal lipooligosaccharide (LOS). Convalescence from disseminated meningococcal disease significantly increased the inhibition by sera of monoclonal antibody (MAb) binding to two of six defined epitopes on the LOS of meningococcal strain 126E, a strain previously shown to express immunogenic LOS epitopes. The inhibited epitopes were defined by MAbs D6A and 6B7, and both were expressed on the 3.6-kDa LOS of strain 126E. The inhibition of the binding of both MAbs by the convalescent sera was similar to that from children who were meningococcal carriers and greater than that by sera obtained from healthy children. These results support the conclusion that the 3.6-kDa LOS molecule of strain 126E expresses two conserved epitopes that are immunogenic in infants and children; this LOS may serve as a vaccine candidate.

Adolescent↗
PubMed1993

Does ozone alleviate AIDS diarrhea?

Five patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) and intractable diarrhea were treated with daily colonic insufflations of medical ozone (oxygen/ozone mixture) for 21-28 days. The daily dose of ozone (O3) ranged from 2.7 to 30 mg. Three of the four patients whose diarrhea was of unknown etiology experienced complete resolution, and one patient had marked improvement. The fifth patient, whose diarrhea was due to Cryptosporidium, experienced no change. No consistent change in the absolute number of helper (CD4) or suppressor (CD8) lymphocytes was detected, and no obvious changes were seen in the PO2 or the results of routine hematologic and blood chemistry studies. Patients had mild to moderate local discomfort during ozone administration early in the course of treatment, but no adverse systemic effects were observed. The results of this series suggest that medical ozone administered by rectal insufflation is simple, safe, and effective. Should this simple treatment be used routinely to treat chronic intractable ARC/AIDS diarrhea?

Acquired Immunodeficiency Syndrome↗
PubMed1993

Investigation of the structural heterogeneity of lipooligosaccharides from pathogenic Haemophilus and Neisseria species and of R-type lipopolysaccharides from Salmonella typhimurium by electrospray mass spectrometry.

Heterogeneity in the lipooligosaccharides (LOS) of pathogenic Haemophilus and Neisseria species is evident from the multiplicity of components observed with electrophoretic analyses. Knowledge of the precise structures that make up these diverse LOS molecules is clearly the key to reaching an understanding of pathogenic processes such as phase variation and molecular mimicry. Except for a few cases, little is known about the specific structural features of LOS that underlie phase variation and molecular mimicry, partly because of the inherent difficulties in the structural elucidation of these complex glycolipids. In the lipopolysaccharides (LPS) from Salmonella typhimurium and Escherichia coli, rough, or R-type, mutants have been isolated that have provided insight into the biosynthetic pathways and associated genetics that control LPS expression. Nonetheless, recent work has shown that these R-type LPS are more complex than originally thought, and significant heterogeneity is still observed, primarily in their phosphorylation states. In order to investigate the structures of LPS and LOS in a more rapid fashion, we have determined the precise molecular weights of LOS (and LPS) preparations from various Haemophilus, Neisseria, and Salmonella species by electrospray ionization-mass spectrometry. The LOS (or LPS) were first O-deacylated under mild hydrazine conditions to remove O-linked esters primarily from the lipid A portion. Under negative-ion conditions, the O-deacylated LOS yield abundant multiply deprotonated molecular ions, (M-nH)n-, where n refers to the number of protons removed and therefore determines the absolute charge state, n = z. Mass spectra from different LOS and LPS preparations have provided detailed information concerning the structural basis for LOS (and LPS) heterogeneity and corresponding saccharide compositions. The identification of sialic acid in the LOS of Haemophilus and Neisseria species and the variable phosphorylation of the core of S. typhimurium LPS have afforded insights into the biosynthetic pathways used by these organisms. Information of this type is important for understanding the underlying genetic and environmental factors controlling LOS and LPS expression.

Antigens, Bacterial↗
PubMed1992

Structural characterization of the cell surface lipooligosaccharides from a nontypable strain of Haemophilus influenzae.

Oligosaccharides released from the lipooligosaccharides (LOS) of Haemophilus influenzae nontypable strain 2019 by mild acid hydrolysis were fractionated by size exclusion chromatography and analyzed by liquid secondary ion mass spectrometry. The major component of the heterogeneous mixture was found to be a hexasaccharide of Mr 1366, which lost two phosphoethanolamine groups upon treatment with 48% aqueous HF. The dephosphorylated hexasaccharide was purified and shown by tandem mass spectrometry, composition analysis, methylation analysis, and two-dimensional nuclear magnetic resonance studies to be Gal beta 1----4Glc beta 1----(Hep alpha 1----2Hep alpha 1----3) 4Hep alpha 1----5anhydro-KDO, where Hep is L-glycero-D-manno-heptose and KDO is 3-deoxy-D-manno-octulosonic acid. An analogous structure containing authentic KDO was generated from LOS that had been HF-treated prior to acetic acid hydrolysis, suggesting that the reducing terminal anhydro-KDO moiety is produced as an artifact of the hydrolysis procedure by beta-elimination of a phosphate substituent from C-4 of KDO. Mass spectral analyses of O-deacylated LOS and free lipid A confirmed that, in addition to the two phosphoethanolamines on the oligosaccharide and two phosphates on the lipid A, another phosphate group exists on the KDO. This KDO does not appear to be further substituted with additional KDO residues in intact H. influenzae 2019 LOS. The terminal disaccharide epitope, Gal beta 1----4Glc beta 1----, of the hexasaccharide is also present on lactosylceramide, a precursor to human blood group antigens. It is postulated that the presence of this structure on H. influenzae LOS may represent a form of host mimicry by the pathogen.

Antigens, Bacterial↗
PubMed1992

Correlation of Pneumocystis carinii cyst density with mortality in patients with acquired immunodeficiency syndrome and pneumocystis pneumonia.

Fifteen percent to 20% of patients with the acquired immunodeficiency syndrome and pneumocystis pneumonia do poorly despite early intervention. It is not known what distinguishes those who die, despite early intervention and aggressive therapy, from those who readily respond to therapy. We used image analysis to determine the relative abundance of cysts within aggregates of Pneumocystis carinii found in induced sputa (21 patients) and bronchoalveolar lavage fluid (14 patients) from 35 patients with pneumocystis pneumonia. We calculated a cyst density (number of cysts per area of aggregate) for each aggregate and a mean cyst density for all of the aggregates on the smear. Six patients died within 2 weeks of diagnosis; four of these six patients who had autopsies all had residual P carinii. The mean cyst density for those who died was 9.7 +/- 3.9 (range, 5 to 15 x 10(-3)). The 29 patients who survived beyond 2 weeks had a mean cyst density of 18.4 +/- 8.7 (range, 5 to 35 x 10(-3); P = .01). Mean cyst density was not influenced by the number of aggregates present in the smear, the variation in cyst density among aggregates in a smear, or the episode of pneumocystis pneumonia. Cyst density determinations alone should not be used to predict outcome for individuals with P carinii pneumonia until further study is completed. Nevertheless, the current study suggests that a low cyst density specimen, which may indirectly indicate a greater proportion of trophozoites compared with a high cyst density specimen, may be associated with an unfavorable outcome in acquired immunodeficiency syndrome-associated pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Sialylation and human neutrophil killing of group C Neisseria meningitidis.

This study describes the association of lipooligosaccharide (LOS) and capsule sialylation with the survival of 25 serogroup C meningococcal strains in phagocytosis assays. Eleven strains isolated from children were of diverse protein serotypes or were nontypeable; 14 were serotype 2b:P1.2 and were isolated from children during or immediately after a focal epidemic in Texas. Degree of endogenous LOS sialylation and amount of sialic acid capsule were associated with each other and with susceptibility to killing by neutrophils for the non-2b:P1.2 strains. The 2b:P1.2 strains as a group had significantly greater survival in the presence of neutrophils than did the non-2b:P1.2 strains. The susceptibility of these strains to killing by neutrophils was not associated with endogenous LOS sialylation or amount of capsule. These data suggest that many virulent strains evade neutrophil killing, either by sialylation or another mechanism. Evasion of neutrophil killing might enhance a strain's epidemic potential.

Child, Preschool↗
PubMed1992

Effect of exogenous sialylation of the lipooligosaccharide of Neisseria gonorrhoeae on opsonophagocytosis.

Serum-sensitive Neisseria gonorrhoeae strains become serum resistant when grown in the presence of a sialic acid precursor, cytidine monophospho-N-acetylneuraminic acid. We examined the abilities of human neutrophils to phagocytose sialylated and nonsialylated gonococci and observed a decrease in the complement-dependent phagocytosis of sialylated gonococci compared with that of nonsialylated gonococci (50.7 versus 25.9% survival at 30 min). This decrease in opsonophagocytosis after sialylation may contribute to the pathogenicity of gonococcal infections.

Humans↗
PubMed1992

Ability of gonococcal and meningococcal lipooligosaccharides to clot Limulus amebocyte lysate.

We investigated whether the striking difference in severity of coagulopathy observed between bacterial sepsis involving Neisseria meningitidis and Neisseria gonorrhoeae species is related to species-dependent abilities to directly activate coagulation. Using lipooligosaccharide (LOS)-activated gelation of Limulus amebocyte lysate, we compared the relative abilities of outer membrane LOS of 10 N. meningitidis and 10 N. gonorrhoeae strains to initiate coagulation. A wide range of procoagulant potencies was observed for each species, and there was significant overlap of potencies between species. Relative biological activities did not correlate with the oligosaccharide components as defined by LOS molecular weight or specific antigenic epitopes. Purified lipid A of two LOS strains of different potency demonstrated relative procoagulant biological activities similar to those of their parent LOSs. When these lipid A preparations were further separated by thin-layer chromatography, the most polar component of each lipid A possessed the majority of the procoagulant activity. We concluded that the ability of neisserial LOS to initiate coagulation of Limulus lysate is a property of the lipid A portion of the molecule and is most likely determined by fine structural differences in the lipid A which are independent of species.

Animals↗
PubMed1992

Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces.

One percent of circulating IgG in humans recognizes galactose alpha 1,3 galactose residues (anti-Gal) and is synthesized in response to stimulation by enteric bacteria. In this study, we found that the prevalence of binding of anti-Gal to blood isolates is significantly higher than its binding to normal stool isolates. When anti-Gal bound onto the lipopolysaccharide of a representative blood isolate, Serratia marcescens #21, it blocked its alternative complement pathway (ACP) lysis and made the organism serum resistant. In contrast, when anti-Gal bound to the capsular polysaccharide of a serum sensitive Serratia, #7, it increased ACP killing of this strain. The mechanism of blockade of ACP lysis by anti-Gal did not involve a decrease in the number of C3 molecules deposited onto Serratia #21 or an inhibition of the binding of C3b to its LPS, nor did it change the iC3b and C3d degradation products of bound C3b or prevent membrane attack complex formation on this organism. Our findings suggest that the effect of anti-Gal on immune lysis is dependent on the bacterial outer membrane structure to which it binds. We postulate that anti-Gal may play a role in the survival of selected Enterobacteriacae in Gram-negative sepsis by blocking ACP-mediated lysis of such bacteria by the nonimmune host, and that this effect depends on where anti-Gal finds its epitope on the bacterial outer membrane.

Complement C3↗
PubMed1992

Detection of antibodies to Pneumocystis carinii in bronchoalveolar lavage fluid by immunoreactivity to Pneumocystis carinii within alveoli, granulomas, and disseminated sites.

Although Pneumocystis carinii pneumonia (PCP) is the most common major opportunistic infection in the acquired immunodeficiency syndrome (AIDS), its immunopathogenesis is not fully understood. It is known that anti-pneumocystis antibodies are present in the sera of individuals with and without PCP. In order to determine whether anti-pneumocystis antibodies are also present in bronchoalveolar lavage fluid (BAL), we looked for them, by immunoreactivity with tissue sections of intra-alveolar P. carinii, in the BAL of (a) HIV-seropositive patients with PCP (n = 18); (b) HIV-seropositive patients without PCP (n = 11); and (c) HIV-seronegative patients with nonpneumocystis lung disease (n = 5). BALs from 19 of 29 HIV-seropositive patients were deficient in at least one isotype (13 with PCP, six without PCP), while only one of five HIV-seronegative patients was deficient. Despite the considerable documentation of atypical presentations of disease caused by P. carinii, little is known concerning the mechanisms involved. To determine whether there is any relationship between BAL anti-pneumocystis antibodies and diverse host responses, we studied antibody binding to P. carinii in different settings. IgG antibodies in BAL bound P. carinii within spleen, liver, skin, and muscle, as well as within pulmonary alveoli and granulomas. However, IgA antibodies in BAL bound intraalveolar and disseminated P. carinii but did not bind to P. carinii within pulmonary granulomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Fungal↗
PubMed1991

Expression of paragloboside-like lipooligosaccharides may be a necessary component of gonococcal pathogenesis in men.

To learn how lipooligosaccharide (LOS) phase variations affect pathogenesis, we studied two male volunteers who were challenged intraurethrally with Neisseria gonorrhoeae that make a single LOS of 3,600 daltons and sequentially followed LOS expression by gonococci as urethritis developed. LOS variation occurred in vivo. Signs and symptoms of gonorrhea began with the appearance of variants making 4,700-dalton LOS that are immunochemically similar to glycosphingolipids of human hematopoietic cells (Mandrell, R.E., J.M. Griffiss, and B.A. Macher. 1989. J. Exp. Med. 168:107) and that have acceptors for sialic acid. A variant that appeared at the onset of leukorrhoea was shed by 34/36 men with naturally acquired gonorrhea at the time they sought medical attention; the other two shed the variant associated with dysuria. None shed the challenge variant. These data show that in vivo phase shifts to higher molecular mass LOS that mimic human cell membrane glycolipids are associated with the development of gonococcal leukorrhea.

Carbohydrate Sequence↗
PubMed1991

Structural determination of oligosaccharides derived from lipooligosaccharide of Neisseria gonorrhoeae F62 by chemical, enzymatic, and two-dimensional NMR methods.

F62 LOS of Neisseria gonorrhoeae consists of two major LOS components; the higher and smaller molecular weight (MW) components were recognized by MAbs 1-1-M and 3F11 respectively. Base-line separation of the two major oligosaccharide (OS) components from F62 LOS was achieved by Bio-Gel P-4 chromatography after dephosphorylation of the OS mixture. The structures of the two major OSs were studied by chemical, enzymatic, and 2D NMR methods [double quantum filtered COSY (DQF-COSY), delayed COSY (D-COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA), pure-absorption 2D NOE NMR] as well as methylation followed by GC/MS analysis. The OS component derived from the MAb 1-1-M defined LOS component was determined to have a V3-(beta-N-acetylgalactosaminyl)neolactotetraose structure (GalNAc is beta 1----3-linked to a neolactotetraose) at one of its nonreducing termini as shown below. The above pentaose is linked to a branched diheptose-KDO core in which a GlcNAc is alpha-linked. The OS component derived from the MAb 3F11 defined LOS component did not have a GalNAc residue. The rest of its structure was identical to that of the OS-1, and a neolactotetraose is exposed at its nonreducing terminus. [formula: see text]

Antigens, Bacterial↗
PubMed1991

The structural basis for pyocin resistance in Neisseria gonorrhoeae lipooligosaccharides.

Pyocin resistance in a strain of Neisseria gonorrhoeae has been found to be associated with structural differences in the oligosaccharide moieties of the gonococcal outer membrane lipooligosaccharides (LOS). N. gonorrhoeae strain 1291 had been treated with several pyocins, usually lethal bacteriocins produced by Pseudomonas aeruginosa, and a series of surviving mutants were selected. The LOS of these pyocin-resistant mutants had altered electrophoretic mobilities in sodium dodecyl sulfate-polyacrylamide gels (Dudas, K. C., and Apicella, M. A. (1988) Infect. Immun. 56, 499-504). Structural analyses of the oligosaccharide portions of the wild-type (1291 wt) and five pyocin-resistant strains (1291a-e) by liquid secondary ion mass spectrometry, tandem mass spectrometry, and methylation analysis revealed that four of the mutant strains make oligosaccharides that differ from the wild-type LOS by successive saccharide deletions (1291a,c-e) and, in the oligosaccharide of 1291b, by the addition of a terminal Gal to the 1291c structure. The composition, sequence, and linkages of the terminal tetrasaccharide of the wild-type LOS are the same as the lacto-N-neotetraose terminus of the human paragloboside (Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4Glc-ceramide), and both glycolipids bound the same monoclonal antibodies O6B4/3F11 that recognize this terminal epitope. None of the pyocin-resistant mutants bound this antibody. The 1291b LOS bound a monoclonal antibody that is specific for Gal alpha 1----4Gal beta 1----4Glc-ceramide (Pk glycosphingolipid) and shared a common composition, sequence, and linkages with this latter glycosphingolipid. Organisms that bound the anti-Pk monoclone occurred at the rate of approximately 1/750 among the wild-type parent strain. This structural information supports the conclusion that treatment with pyocin selects for mutants with truncated LOS structures and suggests that the oligosaccharides contained in the LOS of the wild-type strain and 1291b mimic those of human glycosphingolipids.

Carbohydrate Sequence↗
PubMed1991

Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule.

We have recently shown that human IgA1 can initiate lysis of group C Neisseria meningitidis via the classical C pathway when bound to specific outer membrane proteins, but that IgA1 can also function as a blocking antibody when bound to the polysaccharide capsule of meningococci. In this report, we further characterized IgA1 blockade by examining the effect of IgA1 on IgG-initiated immune lysis of group C meningococci. We purified IgG and monomeric IgA1 from either convalescent group C meningococcal case sera or tetravalent (A, C, Y, W135) polysaccharide vaccinate sera. In the absence of IgA1, IgG initiated complete lysis (greater than 99%) of strains 118V (C:P3,4:L2,4) 126E (C:P3:L1,8), and 35E (C:P5:L2). Addition of IgA1 to the bactericidal reaction mixture completely blocked the lytic function of IgG. Removal of the Fc portion of IgA1 with either pepsin or IgA1 protease did not affect blockade. Both the F(ab')2 and Fab derivatives of IgA1 blocked lysis quantitatively as well as intact IgA1. The Fc fragment produced by IgA1 protease cleavage neither increased nor decreased Fab-mediated blockade. IgA1 and its Fab and F(ab')2 fragments blocked IgG-initiated lysis via either the classical pathway in factor B-depleted and in properdin-deficient serum, the alternative pathway in MgEGTA-chelated serum, or both pathways combined. Absorption of the IgA1 and IgG with alum-bound group C polysaccharide completely removed blocking and lytic activity, respectively, indicating that both the blocking IgA1 and the lytic IgG were specific for the group C capsule. Blocking by IgA1 was a linear function of the polysaccharide Ag-binding capacity (ABC) ratio of blocking IgA1 to lytic IgG. Complete blockade was observed at an ABC ratio of 5.5. At ABC ratios of 3.3 and 4.4, IgA1 affected significant blockade whether added previous to, concurrent with, or subsequent to sensitization of the organisms with IgG. With the use of a C polysaccharide ELISA, we found that the binding of IgA1 to the group C capsule in the presence of IgG exhibited positive cooperativity and therefore that blockade was independent of the ability of IgA1 to directly compete with IgG for binding to epitopes within the group C capsule. We conclude that IgA1, when bound to the group C polysaccharide capsule, can block IgG-initiated lysis of group C meningococci through either the classical or the alternative pathway before or after the organism is exposed to IgG, and that blockade is an Fc-independent event.

Antibodies, Bacterial↗
PubMed1991

Lysis of Neisseria gonorrhoeae initiated by binding of normal human IgM to a hexosamine-containing lipooligosaccharide epitope(s) is augmented by strain-specific, properdin-binding-dependent alternative complement pathway activation.

We studied the specificity of naturally acquired IgM bactericidal for strains of Neisseria gonorrhoeae that varied in sensitivity to the lytic action of normal human serum (NHS) and the relative ability of these strains to deplete the classical (CP) and alternative (ACP) C pathways. Lysis of both highly sensitive and relatively insensitive strains was inhibited by the same gonococcal lipooligosaccharides (LOS), as well as by Salmonella minnesota Re LOS and three hexosamine-containing glycose polymers. A polymer of N-acetylgalactosamine phosphate was the most inhibitory; a polymer of N-acetylglucosamine phosphate only partially inhibited. Neither 3-deoxy-D-manno-octulosonic acid (dOc1A) nor a polymer that contained dOc1A but not hexosamine inhibited NHS lysis. A co-polymer of N-acetylgalactosamine-dOc1A inhibited both bactericidal activity and the binding of IgM to the LOS of a highly serum-sensitive (sers) gonococcal strain. Carboxyl reduction of the dOc1A in this polymer did not affect its inhibitory capacity for gonococcal antibody, but abolished its binding to homologous antibody induced by vaccination. CP activity was not affected by vaccination. CP activity was not affected by absorption of NHS with gonococcal strains, whereas ablation of CP activity markedly but variously diminished lytic activity for highly sers strains. ACP activity was variously depleted by gonococcal strains, and the proportion of bacteria that could be lysed through the ACP varied among strains and among different populations of a given strain. The titer at which a strain was sensitive to NHS lysis was a function of its ACP consumption (p = 0.006), which accounted for 70% of the differences in titer among strains. Analyses of the absorbed sera revealed that the gonococci had variously depleted properdin from NHS as assessed by using an Ag-capture solid-phase RIA. Addition of purified properdin to absorbed sera restored ACP activity to normal levels. Western immunoblots of gonococcal lysates showed that purified properdin bound directly to a 39-kDa outer membrane protein. We conclude that both CP activation by IgM binding to LOS epitopes, one of which contains hexosamine, and ACP activation, which is a function of strain-specific direct binding of properdin, can initiate lysis of sers strains and that ACP activation, also enhances lysis and accounts for variations in sensitivity of sers strains.

Antigens, Bacterial↗
PubMed1991

Meningococcal molecular mimicry and the search for an ideal vaccine.

The carbohydrates expressed on the surface of meningococcal strains of groups B and C mimic those commonly found on human cells and thus are not functionally antigenic in infancy. In order to develop an effective vaccine, it will be necessary to find ways of circumventing this molecular mimicry. Three possible ways of achieving this are discussed. (i) The surface polysaccharides can theoretically present conformationally different epitopes, some of which might be recognized as antigenic by the host. Experimental evidence is presented that such differences do indeed exist; what is needed is to determine which of these conformations are unique to the organism and hence potentially antigenic. (ii) Precursors of the surface lipooligosaccharides may be unable to mimic human antigens, and so may be potential candidates for vaccine development. (iii) Natural immunity to some strains of meningococci develops in young children who are colonized with strains of Neisseria lactamica, and it is possible that its development could be enhanced by widespread intentional colonization by N. lactamica strains that are particularly efficient inducers of broad immunity.

Bacterial Vaccines↗