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Humoral immune responses to the Plasmodium falciparum antigen Pf155 RESA in adults with differential clinical conditions from an Indian zone where malaria is endemic.

Ring infected erythrocyte surface antigen of Plasmodium falciparum (Pf155/RESA) has been considered as a vaccine candidate. However, the relative immunogenicity of this antigen has not been studied in Indian populations. Pf155/RESA was investigated for its immunogenicity by studying humoral immune responses against Pf155/RESA and Pf155/RESA derived peptides (P1, P2 representing immunodominant epitopes from the 3' and P3 from the 5' repeat regions) by erythrocyte membrane immunofluorescence (EMIF) assay and by enzyme linked immunosorbent assay (ELISA) in P. falciparum primed donors living in hyperendemic malarious areas (Orissa State, India) where P. falciparum infections are highly prevalent. Subjects of different clinical status namely acute (A), clinically immune (CI) and acute with history of repeated P. falciparum infections (R) were included in this study. All the donors were seropositive against the crude antigen. There was considerable variation in the responses among the donors. While humoral responses in the plasmas against the P2 peptide (EENV)4 were significantly higher in magnitude and in frequency in the CI donors than in the A donors, no positive response was seen in the R donors. The responses to the peptides P1 (EENVEHDA)2 and P3 (DDEHVEEPTVA)2 were poor both in the A and in the CI groups. Whereas, most of the R donors were seropositive against the P3. The present results indicate that Pf155/RESA contains B cell epitopes which were recognized differently by the immune system of individuals living in malaria-hyperendemic areas of India who have been primed by natural infection. Our studies also suggest that in order to investigate the possible functional role of a given antigen, study of immune responses against the antigen in donors of different clinical status may be useful.

Adult↗

Vaccine strategies: selective elicitation of cellular or humoral immunity?

The discovery of immunoregulatory cytokines and the fact that they modulate the cellular and humoral arms of the immune system, generally in opposing directions raises fundamental questions concerning vaccine development. Because antibiotic-resistance infectious organisms are appearing at an increasingly rapid rate, more emphasis will need to be placed on prevention of infection/disease via immunization and less on post-infection antibiotics. To accomplish this task effectively, immune regulation should be integrated into vaccine design. Here we consider the opposing potentials of cytokine-regulated cellular and humoral immunity, and question whether the "best of both worlds' is possible or desirable.

Animals↗

Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine.

PURPOSE: Although the improved overall survival (OS) of patients who receive Canvaxin (CancerVax Corp, Carlsbad, CA) polyvalent vaccine (PV) immunotherapy for metastatic melanoma has been correlated with cellular and humoral immune responses, the mechanisms of vaccine immunotherapy for early-stage melanoma are unclear. Specific immune responses to tumor-associated antigens might correlate with disease-free survival (DFS) and OS in patients receiving adjuvant PV therapy for primary melanoma. PATIENTS AND METHODS: Eighty-three patients received PV plus bacille Calmette-Guérin after wide excision of American Joint Committee on Cancer stage II melanoma. Humoral and cellular responses during the first 12 weeks of adjuvant immunotherapy were assessed by serum antibody titers to a tumor-associated 90-kd glycoprotein antigen (TA90) expressed by PV, and by delayed-type hypersensitivity (DTH) skin testing with PV (PV-DTH). RESULTS: At a median follow-up period of 46.6 months (range, 10.7 to 93.6 months), an increased PV-DTH response seemed to be associated with improved 5-year DFS (54% v 20%) and 5-year OS (75% v 60%), but the correlations were not statistically significant. Anti-TA90 immunoglobulin (Ig) M levels > or = 1:800 were significantly correlated with improved 5-year DFS and improved 5-year OS, and multivariate analysis identified anti-TA90 IgM as an independent prognostic factor for OS and DFS. CONCLUSION: These findings suggest that an increased IgM response in patients receiving PV therapy for stage II melanoma is associated with decreased recurrence and improved survival.

Antibody Formation↗

Humoral immune factors modulated by copper and chitosan in healthy or parasitised carp (Cyprinus carpio L.) by Ptychobothrium sp. (Cestoda).

As an environmental protection point of view, the potential toxicity of chitosan on aquatic animal health, alone or associated with copper must be investigated. Fish possess defence mechanisms to counteract the impact of toxics. The non-cellular and non-specific immune defences (total immunoglobulin, ceruloplasmin, lysozyme and potential killing activity of phagocytic cells) can be modulated by the potential environmental pollutants but also by natural stimulants such as bacteria, viruses or parasites. In this study, we investigate the potential toxicity of copper (0.1 and 0.25 mg/L) or chitosan (75 and 150 mg/L) and the combination copper and chitosan (0.1 and 75 mg/L, respectively) on two groups of carp: healthy or parasitised by Ptychobothrium sp. Fish exposed to water-soluble chitosan for 96 h had significantly high levels of natural antibodies in plasma. Moreover, activities of lysozyme and ceruloplasmin were also increased in plasma after the same treatment. The exposition of fish to copper have shown apparently contradictory effects on the immune parameters measured but, significant increase of this bacteriolytic activity was observed, particularly in head kidney after 4 days of treatment of fish with copper. The two products may induce separately an acute, short and local inflammatory acute phase response by stimulating some components of the innate immune response of healthy fish. The mixture seems to reduce the impact of the each product due to the physical and chemical properties of chitosan to complex with copper. The responses of humoral immune factors of treated carp was modulated by the presence of the parasite, as shown by the high elevation of lysozyme activity observed in parasitised carps after exposition to copper and by increases in natural antibodies levels observed in parasitised carp treated with the copper-chitosan mixture. This could indicate an additive effect on the stress response mediated by parasite. It occurred a greater stress response in the parasitised group than healthy group exposed to the same treatment evoking an additive effect. So, it is important to specify the health status of organisms to understand responses of immunological markers in fish.

Animals↗

A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-specific humoral immune responses in cynomolgus macaques.

Cynomolgus macaques were immunized by either the intramuscular (i.m.) or intranasal (i.n.) route with a HIV-1 peptide-based immunogen (C4-V3 89.6P) alone, or formulated with novel adjuvants to evaluate the ability of the adjuvants to augment peptide-specific systemic and mucosal immune responses. A mutant cholera toxin, CT-E29H, or the combination of recombinant human IL-1alpha (rhIL-1alpha) protein and recombinant human GM-CSF (rhGM-CSF) protein were tested as adjuvants for i.n. immunization, while a stable emulsion of a synthetic monophosphoryl lipid A (MPL) analogue (RC529-SE) plus rhGM-CSF protein was tested as an adjuvant for i.m. immunization. Macaques immunized i.n. with peptide alone failed to elicit an anti-C4-V3 89.6P antibody response in serum. In contrast, all the tested peptide/adjuvant formulations elicited peptide-specific immune responses. RC529-SE/rhGM-CSF elicited the highest peak anti-peptide IgG geometric mean titer in serum (1:32,768 at week 25) followed by rhIL-1alpha/rhGM-CSF (1:1217 at week 10) and CT-E29H (1:256 at week 25). Measurable SHIV neutralizing antibody responses were detectable in only one macaque immunized i.m. with peptide formulated with RC529-SE/rhGM-CSF. Macaques immunized by the i.n. route with peptide in combination with CT-E29H failed to elicit measurable antibody responses at nasal or genital mucosal surfaces. In contrast, antibody responses at the nasal and genital mucosa were detected in macaques immunized by the i.n. route with peptide in combination with rhIL-1alpha/rhGM-CSF. However, antibody responses at the nasal and genital mucosa were highest in macaques immunized parenterally with peptide in combination with the adjuvants RC529-SE/rhGM-CSF. These results suggest that parenteral vaccine administration in combination with the appropriate adjuvant formulation can elicit vaccine-specific humoral immune responses in both systemic and mucosal compartments.

AIDS Vaccines↗

The GATA factor Serpent is required for the onset of the humoral immune response in Drosophila embryos.

Innate immunity in Drosophila is characterized by the inducible expression of antimicrobial peptides. We have investigated the development and regulation of immune responsiveness in Drosophila embryos after infection. Immune competence, as monitored by the induction of Cecropin A1-lacZ constructs, was observed first in the embryonic yolk. This observation suggests that the yolk plays an important role in the humoral immune response of the developing embryo by synthesizing antimicrobial peptides. Around midembryogenesis, the response in the yolk was diminished. Simultaneously, Cecropin expression became inducible in a large number of cells in the epidermis, demonstrating that late-stage embryos can synthesize their own antibiotics in the epidermis. This production likely serves to provide the hatching larva with an active antimicrobial barrier and protection against systemic infections. Cecropin expression in the yolk required the presence of a GATA site in the promoter as well as the involvement of the GATA-binding transcription factor Serpent (dGATAb). In contrast, neither the GATA site nor Serpent were necessary for Cecropin expression in the epidermis. Thus, the inducible immune responses in the yolk and in the epidermis can be uncoupled and call for distinct sets of transcription factors. Our data suggest that Serpent is involved in the distinction between a systemic response in the yolk/fat body and a local immune response in epithelial cells. In addition, the present study shows that signal transduction pathways controlling innate and epithelial defense reactions can be dissected genetically in Drosophila embryos.

Animals↗

Humoral immune response in human tuberculosis: immunoglobulins G, A, and M directed against the purified P32 protein antigen of Mycobacterium bovis bacillus Calmette-Guérin.

The P32 protein antigen of Mycobacterium bovis BCG, identified as antigen 85A in the BCG reference system, was used to investigate the humoral immune response in human tuberculosis (TB). Immunoglobulin G (IgG), IgA, and IgM directed against P32 were measured by an enzyme-linked immunosorbent assay. Mean IgG and IgA antibody levels differed significantly (P less than 0.001) between active-TB patients (50 untreated and 52 treated) and healthy control subjects (111 unvaccinated tuberculin negative, 38 unvaccinated tuberculin positive, and 72 recently BCG vaccinated). Mean IgG antibody levels, but not mean IgA antibody levels, were higher (P less than 0.05) in patients with positive microscopic examination for acid-fast bacilli than in patients with negative microscopic examination. A positive relation was found between mean levels and the extent of disease. There was no difference in mean IgM antibody levels between patients and controls. By setting the upper normal limit at the 95th percentile of the 221 healthy subjects, the sensitivities were 46% in untreated and 63% in treated patients for IgG and 30 and 50%, respectively, for IgA. Of the untreated patients, 56% were positive for either IgG or IgA antibodies. Among the untreated patients with negative direct smear, 35% were positive for IgG and 24% were positive for IgA. When both immunoglobulin classes were combined, the serological test was positive in 47% of those patients. Neither naturally acquired tuberculin hypersensitivity nor BCG vaccination affected positivity frequencies in healthy subjects. Only active TB seemed to induce significant anti-P32 antibody levels and to be associated with positivity. A serological test with P32 as the antigen might therefore be helpful for the rapid diagnosis of TB.

Adolescent↗

Blockade of central and peripheral luteinizing hormone-releasing hormone (LHRH) receptors in neonatal rats with a potent LHRH-antagonist inhibits the morphofunctional development of the thymus and maturation of the cell-mediated and humoral immune responses.

The development of the thymus and the hypothalamic-pituitary-gonadal axis are linked by bidirectional hormonally mediated relationships. In the present study, the direct involvement of the neuropeptide LHRH in the maturation of the thymus and development of the cell-mediated and humoral immune responses were assessed after treatment of neonatal (from post-natal day 1-day 5) female rats with a potent LHRH-antagonist (LHRH-anta, p-Glu-D-Phe 2.6,Pro3-LHRH, 50 micrograms/rat), and the effects compared to those resulting from neonatal castration. Whereas in control animals the maturation of mitogenic potential in thymocyte cultures showed a progressive and age-dependent increase, reaching a maximal activity at 30 days of age and then decreasing after puberty onset, in LHRH-anta-treated rats, the thymocyte's proliferative response was completely blocked at 7 days of age and remained very low at each time interval studied, until 3 months of age. A similar effect of the LHRH-anta treatment on splenocyte cultures was measured. Moreover, a reduced percentage of the T-helper lymphocyte subpopulation followed LHRH-anta administration. By contrast, in neonatally castrated rats, blastogenic activity was significantly higher, compared to control cultures, at each stage studied. Treatment with LHRH-anta produced a significant decrease in thymus wt, an alteration of the maturational pattern characterized by a cellular monomorphism, reduced thymocyte volume, reduction of the cortical area, and depauperation of the epithelial microenvironment. Moreover, a morphometric analysis revealed a selective decrease in the large lymphoid cell population of the subcapsular cortex at 7 and 15 days. On the other hand, neonatal castration produced an opposite effect, leading to a marked hypertrophy of the cortical area, and counteracted the post-puberal thymus atrophy. When LHRH-anta-treated adult (3-month-old) rats were challenged with an antigenic stimulus (multiple sc injections of complete Freund adjuvant and BSA) and antibody (anti-BSA antibodies of the immunoglobulin G class) production measured in the serum after 15 days, a marked and significant decrease in immunoglobulin G levels was observed, compared to the values measured in untreated control. The described immune deficiencies in LHRH-anta-treated rats were associated with a clear inhibition of sexual maturation. This study clearly indicates that the blockade of central and peripheral LHRH receptors during a critical period for maturation of both hypothalamus-hypophyseal-gonadal axis and brain-thymus-lymphoid axis dramatically impairs immune system development, suggesting a potential role of the neuropeptide LHRH in the bidirectional programming of both neuroendocrine and immune functions.

Animals↗

[Multi-year observations of the humoral immunity status of patients with tick-borne encephalitis in 3 endemic regions].

Analysis of the results of the laboratory diagnosis of tick-borne encephalitis (TBE) by HI test over many years proved a statistically significant decrease by the 80's in the intensity of humoral immunity in the subjects with a history of tick-borne encephalitis in Kemerovo Province, Udmurtia and Latvia. A decrease in antihemagglutinin levels in the blood of convalescents after TBE was detected in endemic foci located in different geographical regions differing by epidemiological parameters; it did not depend on the portion of infected ticks and ratio of the clinical forms of the disease in a focus. Parallel tests by HI of the diagnostic value of several antigens of TBE virus strains isolated from different sources in different regions with sera from TBE patients revealed no differences among them. The antigenic activity of the strains in HI test did not depend on the source and region of isolation (Kemerovo Province, Udmurtia and Latvia).

Antibodies, Viral↗

Western blot analysis of humoral immune response to Leishmania donovani antigens in patients with post-kala-azar dermal leishmaniasis.

Sera from 32 Indian patients with post-kala-azar dermal leishmaniasis (PKDL) were examined for antibodies by immunoblot analysis using an antigen extract of Leishmania donovani. The study revealed that the humoral immune response in PKDL patients was quite distinct compared to that in kala-azar patients. Antibodies to 3 antigens of L. donovani (molecular sizes 110, 65 and 38-42 kDa) were predominant in a majority (78%) of PKDL patients. The most important finding was the consistent recognition of 2 parasite antigens (of 110 and 65 kDa) by PKDL sera; antibodies to the 110-kDa antigen were detectable in 97% of cases, while antibodies to the 65-kDa antigen were detectable in 100% of cases that were examined. None of the 18 cases of leprosy, 10 of vitiligo, or the 30 healthy persons included in the study showed antibodies to these 2 antigens. Thus Western blot analysis provided a highly sensitive test for PKDL patients. Further, it led to the identification of 2 parasite antigens (110 and 65 kDa) that elicit an antibody response in 97-100% of PKDL patients. Purified or recombinant versions of these proteins deserve consideration as potential target antigens in development of simpler, highly specific and sensitive serodiagnostic tests for PKDL.

Adolescent↗

Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques.

MOTIVATION: We present a study of antigen expression signals from a newly developed high-throughput protein microarray technique. These signals are a measure of antibody-antigen binding activity and provide a basis for understanding humoral immune responses to various infectious agents and supporting vaccine and diagnostic development. RESULTS: We investigate the characteristics of these expression profiles and show that noise models, normalization, variance estimation and differential expression analysis techniques developed in the context of DNA microarray analysis can be adapted and applied to these protein arrays. Using a high-dimensional dataset containing measurements of expression profiles of antibody reactivity against each protein (295 antigens and 9 controls) in 42 malaria (Plasmodium falciparum) protein arrays derived from 22 donors with various clinical presentations of malaria, we present a methodology for the analysis and identification of significantly expressed antigens targeted by immune responses for individual sera, groups of sera and across stages of infection. We also conduct a short study highlighting the top immunoreactive antigens where we identify three novel high priority antigens for future evaluation. AVAILABILITY: All software programs (in R) used for the analysis described in this paper are freely available for academic purposes at www.igb.uci.edu/servers/servers.html.

Algorithms↗

Development and distribution of cysts of an avirulent strain of Toxoplasma and the humoral immune response in mice.

An avirulent T. gondii strain isolated from a owl (Glaucidium brasilianum) produces randomly distributed cysts in the brain of mice which can survive to inocula as high as 1000 oocysts. Cysts appeared for the first time after 15 days of infection. Regarding to humoral immunity development due to our TCR-2 strain, detectable antibodies were found after 12 days of infection.

Animals↗

Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity.

B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) superfamily. BLyS stimulates proliferation of, and immunoglobulin production by, B cells. However, the relative importance of BLyS in physiological B cell activation is unclear. We identified a B cell receptor for BLyS through expression cloning as TACI, an orphan TNF receptor homologue of unknown function. Binding of BLyS to TACI activated signaling by nuclear factor-kappa B (NF-kappa B). In vitro soluble TACI-Fc fusion protein blocked BLyS-induced NF-kappa B activation in B lymphoma cells and IgM production in peripheral blood B cells. In vivo treatment of immunized mice with TACI-Fc inhibited production of antigen-specific IgM and IgGI antibodies and abolished splenic germinal center (GC) formation. Thus, BLyS activity must play a critical role in the humoral immune response.

Animals↗

Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity.

Individuals of many vertebrate species undergo seasonal changes in immune function in addition to marked seasonal changes in reproductive, metabolic, and other physiological processes. Despite growing evidence that photoperiod mediates seasonal changes in immunity, little is known regarding the neuroendocrine mechanisms underlying these changes. Enhanced immune function in short days is correlated with increased duration of nightly melatonin secretion, and recent studies indicate that melatonin can act directly on immune cells to enhance immune function. It remains unknown, however, which melatonin receptor subtype mediates immune enhancement by melatonin. The present study examined the contribution of specific melatonin receptor subtypes, mt1 (Mel 1a) and MT2 (Mel 1b), in mediating melatonin-induced enhancement of cell-mediated and humoral immune function in mice. Melatonin enhanced both splenocyte proliferation and anti-keyhole limpet hemocyanin (KLH) IgG concentrations in both wild-type (WT) and mice lacking a functional gene for melatonin receptor mt1 (mt1 -/-), suggesting that the mt1 receptor does not mediate these responses. In addition, luzindole, an MT2 receptor antagonist, attenuated melatonin-induced enhancement of splenocyte proliferation in both WT and mt1 -/- mice. Taken together, these results suggest that receptor subtype mt1 is not necessary for mediating melatonin-induced enhancement of immune function and provide the first evidence for a specific melatonin receptor subtype, MT2, that may be involved in melatonin-induced immune enhancement.

Animals↗

Current chemotherapy protocols for childhood acute lymphoblastic leukemia induce loss of humoral immunity to viral vaccination antigens.

OBJECTIVE: To evaluate viral vaccination immunity and booster responses in children treated successfully for acute lymphoblastic leukemia by chemotherapy and to study the response to treatment of antibody-producing plasma cells that are important for persistence of humoral immunity. METHODS: Forty-three children who were in continuous first remission for a median of 5 years (range: 2-12 years) were studied. Before the leukemia was diagnosed, all children had been immunized against measles, mumps, and rubella according to the Swedish National immunization program. We analyzed levels of serum antibodies against measles and rubella by enzyme immunoassays. Avidity tests for measles antibodies were concomitantly performed by enzyme-linked immunosorbent assay for measles virus immunoglobulin G detection. The proportion of plasma cells in bone marrow was studied by flow cytometry at different times during treatment and follow-up. Children who lacked protective levels of antibodies to vaccination antigens were reimmunized. Serum was collected 3 months after immunization to assess vaccination responses. RESULTS: After completion of the treatment, only 26 of the 43 children (60%) were found to be immune against measles and 31 (72%) against rubella. The proportion of bone marrow plasma cells decreased during treatment but returned to normal after 6 months. Revaccination caused both primary and secondary immune responses. Six of the 14 children without immunity failed to achieve protective levels of specific antibodies against measles and 3 against rubella. CONCLUSIONS: Our finding of loss of antibodies against measles and rubella in children treated with intensive chemotherapy suggests that reimmunization of these patients is necessary after completion of the treatment. To determine reimmunization schedules for children treated with chemotherapy, vaccination responses need to be studied further.

Adolescent↗

Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula.

BACKGROUND: Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF). METHODS: Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points. RESULTS: A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months. CONCLUSIONS: Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.

Animals↗

Humoral immunity in experimental immune carditis.

An experimental model of carditis has been produced in the rhesus monkey by giving 12 weekly injections of a streptococcal membrane antigen. There was histological evidence of focal myocarditis, subendocardial infiltration with lymphomononuclear cells and in one animal myocardial granuloma formation. No valvular lesions were seen. Humoral immune responses monitored throughout the experiment showed that anti-heart antibodies appeared in circulation after the 2nd injection, attained maximal titres by the 6th injection, and thereafter the titres declined. The anti-membrane antibodies appeared slightly later and these titres kept rising till sacrifice. By the 6th injection there was evidence of complement consumption and appearance of circulating immune complexes. It is concluded that these immunological responses might have a role to play in the pathogenesis of carditis.

Animals↗

Persistence of cell-mediated and humoral immune responses in healthy children immunized with live attenuated varicella vaccine.

Two hundred fourteen healthy seronegative children immunized with various doses of Oka/Merck varicella vaccine were studied for persistence of varicella-zoster virus (VZV)-specific lymphocyte proliferation and antibodies to VZV as determined by a glycoprotein (gp) ELISA. Of the 140 vaccinees tested for VZV-specific lymphocyte proliferation, 94% had positive responses, with a mean stimulation index of 8.9 (range, 3.0-44.6). Of 214 tested by gpELISA, 95% were positive for up to 6 years after immunization; the geometric mean titer was 30.2 (range, 1.3-3510.0). Of 122 individuals tested both by ELISA and for VZV-specific lymphocyte proliferation, 91% had persistence of both responses. Persistence of cellular and humoral immune responses in a large percentage of vaccinees for up to 6 years after immunization with Oka/Merck varicella vaccine suggests that protection against severe varicella is likely to be similarly long-lasting.

Adolescent↗