Development and persistence of local and systemic antibody responses in adults given live attenuated or inactivated influenza A virus vaccine.

An enzyme-linked immunosorbent assay was used to measure nasal-wash and serum isotype-specific hemagglutinin antibody responses in 109 seronegative (hemagglutination-inhibiting titer less than or equal to 1:8) adults vaccinated intranasally with live attenuated A/Washington/897/80 (H3N2) or A/California/10/78 (H1N1) cold-adapted (ca) virus or with licensed subvirion vaccine subcutaneously. Live and inactivated virus elicited serum immunoglobulin A (IgA) responses in 83 and 96% of vaccinees, respectively, and elicited serum IgG responses in 72 and 100% of vaccinees. Inactivated virus induced higher titers of serum antibodies than did live virus and stimulated a nasal-wash IgG response more often than did live virus (94 versus 59%, P less than 0.01). In contrast, only 38% of inactivated virus vaccinees had local IgA responses compared with 83% of live virus vaccinees. Serum IgA and IgG and nasal IgG antibody titers remained elevated above prevaccination levels for at least 6 months in most of the live and inactivated vaccine responders, but the mean level of local IgA antibody induced by infection with live virus vaccine, in particular, decreased substantially. Considered in the context of previous work, the finding that live virus vaccine induced relatively long-lasting antibody in both local and serum compartments suggested that this vaccine may be a suitable alternative to inactivated vaccine for use in healthy persons.     

Measles immunity and response to revaccination of a young adult population in Israel

In order to evaluate the true immune status and the effect of revaccination on a young adult population, we collected serum samples from 289 military recruits who were vaccinated during an outbreak in 1991. Most vaccinees, age 18–25 years, had apparently been immunized once before as infants. Sera collected just prior to the vaccination and 14 and 28 days afterwards were tested for measles antibodies by hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA)-IgM. Before vaccination, 46 (15.9%) of the subjects had no HI antibodies, (<1:4) and 48 (16.6%) had borderline (1:4) HI titer. Following vaccination, only ten (3.5%) remained negative and 19 (6.6%) had borderline titer. The increase in HI antibody titer was inversely proportional to the prevaccination titer, and 159 subjects (55.0%) showed no increase at all. The geometric mean titer (GMT) rose from 9.14 to 21.47. Among the prevaccination-negative subjects (HI <1:4) 28 (60.9%) reached a postvaccination titer of ≥ 1:8, and eight (17.4%) reached a titer of 1:4. Twelve (26.1%) of the negative subjects seroconverted and developed IgM, 16 (35%) seroconverted without IgM, and 18 (39%) remained negative and did not develop IgM. A group of eight vaccinees with prevaccination titer of ≥ 1:4 developed IgM. Some were probably infected by the circulating wild-type virus prior to the vaccination. Thus, a total number of 20 of the 289 subjects studied (6.9%) had true negative preimmune status as judged by the IgM test. However, the vaccination campaign prevented further measles cases, apparently by increasing the population's immunity, particularly in individuals with very low titers or without measles antibodies. © 1996 Wiley-Liss, Inc.     

Increased sensitivity and reduced specificity of hemagglutination inhibition tests with ether-treated influenza B/Singapore/222/79

Hemagglutination inhibition (HI) tests against whole virus (WV) influenza B/Singapore/222/79 antigen detected prevaccination serum antibody in only 15 (20%) of 50 predominantly elderly volunteers and fourfold or greater titer rises in only three (6%) after they received 1981-1982 trivalent influenza vaccine containing antigens of this virus. HI titers against ether-treated (ET) B/Singapore/222/79 were about eightfold higher than those against WV antigen and were comparable to microneutralization titers against this virus. The ET HI detected prevaccination antibody in 84%, a postvaccination titer rise in 32%, and a final titer of 80 or higher in 66%. Among 51 additional persons with known or presumed influenza B virus infections early in 1982, ET B/Singapore/222/79 was also more sensitive than WV for serodiagnosis (69 versus 49%), but eight persons with both WV and ET B/Singapore/222/79 HI responses also had an HI titer rise to WV A/Brazil/11/78 (H1N1) antigen. Conversely, among 14 college students with febrile, culture-proven influenza A (H1N1) infections early in 1982, 6 (43%) developed HI titer rises to ET B/Singapore/222/79 with no other serological evidence of influenza B virus infection. Moreover, young adult volunteers with mild experimental influenza A (H1N1) infections also exhibited a 17% (3 of 18) incidence of ET B/Singapore/222/79 HI titer rises, versus none in matched, uninfected volunteers. These data indicate that ET B/Singapore/222/79 virus has increased sensitivity but reduced specificity compared to WV as an HI antigen and that caution is needed in interpretation of a single HI test for serodiagnosis, whether with WV or ET antigen.     

Local and systemic antibody responses in high-risk adults given live-attenuated and inactivated influenza A virus vaccines.

Forty seropositive older adults with chronic diseases were vaccinated intranasally with either influenza A/California/10/78 (H1N1) (CR37) or influenza A/Washington/897/80 (H3N2) (CR48) virus. No clinically significant decrements in pulmonary function occurred postvaccination. Eight (62%) recipients of CR37 virus and 16 (59%) recipients of CR48 virus became infected with vaccine virus, as indicated by a fourfold rise in nasal wash immunoglobulin G (IgG) or IgA antibody titer, a fourfold rise in serum antibody titer, isolation of vaccine virus from nasal washings, or all of these. Within 2 years after cold-recombinant virus vaccination, 29 vaccinees received trivalent inactivated influenza virus vaccine parenterally. After inactivated virus vaccination, 23 (79%) vaccinees developed a fourfold rise in nasal wash or serum antibody titer to H1 antigen and 24 (83%) developed a fourfold rise in nasal wash or serum antibody titer to H3 antigen. Significantly more cold-recombinant virus vaccinees developed a fourfold rise in nasal wash IgA antibody to H1 or H3 hemagglutinin compared with inactivated virus vaccinees (17 [43%] versus 9 [17%], P = 0.01). We conclude that these cold-recombinant virus vaccines are safe and immunogenic in seropositive older high-risk adults and more often induced a nasal wash IgA antibody response than the inactivated virus vaccine.     

Systemic and local antibody responses in elderly subjects given live or inactivated influenza A virus vaccines.

Intranasal live attenuated cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant virus and parenteral inactivated influenza A/Taiwan/1/86 (H1N1) virus were given alone or in combination to 80 ambulatory elderly subjects. An enzyme-linked immunosorbent assay was used to measure hemagglutinin-specific (HA) antibodies in serum and nasal wash specimens collected before vaccination and 1 and 3 months later. Serum immunoglobulin G (IgG) and nasal wash IgA HA responses were elicited in 56 and 20%, respectively, of 25 inactivated-virus vaccinees and in 67 and 48%, respectively, of 27 recipients of both vaccines but in only 36 and 25%, respectively, of 28 vaccinees given live virus alone. Inactivated virus, administered alone or with live virus vaccine, induced higher titers of serum antibody than did the live virus alone. In contrast, nasal IgA HA antibody was elicited more often and in greater quantity by the vaccine combination than by either vaccine alone. Despite these differences, the peak titers of local antibody mounted by each group of vaccinees were similar. By 3 months postvaccination, serum IgG and nasal IgA HA antibody titers remained elevated above prevaccination levels in 50 and 17%, respectively, of the inactivated-virus vaccinees and in 46 and 23%, respectively, of recipients of both vaccines but in only 19 and 7%, respectively, of the live-virus and systemic antibodies, if vaccinees. The finding that live ca influenza A virus induced short-lived local and systemic antibodies, if confirmed, suggests that live virus vaccination may not be a suitable alternative or adjunct to inactivated virus vaccination for the elderly.     

Longitudinal course of human metapneumovirus antibody titers and reinfection in healthy adults

The purpose of this study was to evaluate the frequency of human metapneumovirus (hMPV) infection in adults and to determine the association between the levels of serum antibody titers and the susceptibility to reinfection. Serum samples collected at the periodic occupational medical checkup for employees of a hospital were subjected to an ELISA test. Of the 289 subjects, 288 (99.7%) had hMPV antibody titers that were more than 1:100 in May 2006. The percentage of subjects with a titer of ≥ 3,200 was significantly higher in adults aged 40-65 years old (30.2-31.5%) compared to young adults 20-39 years old (13.6%) (P < 0.05). To investigate the longitudinal course of the hMPV antibody titer, a total of 649 serum samples collected from 59 subjects who had participated in all biannual medical checkups between 2001 and 2006 were tested. We found that ten serum pairs showed a greater than fourfold increase in hMPV antibody titers. Additionally, the 5-year reinfection rate was estimated at 16.9% (10 of 59 subjects). The baseline titer before the fourfold increase ranged from 1:100 to 1:3,200, and the titer returned to baseline levels 2 or 3 years after the fourfold increase. The antibody titer of the person with the baseline titer of 1:100 showed a greater than fourfold increase twice within a year. Sixty to 80% of adults had an ELISA titer of 1:800 to 1:1,600, suggesting that such an antibody titer is not enough to protect from hMPV infection and that reinfection could occur among adults.     

Single radial hemolysis test for rubella immunity and recent infection.

The single radial hemolysis (SRH) test was compared with the hemagglutination inhibition (HI) test for establishing rubella immune status and diagnosing recent infection. Correlation between mean SRH diameters and HI titers greater than or equal to 1:8 was high (R = 0.99). It is suggested that a level of greater than or equal to 5 IU represents low-level antibody and that greater than or equal to 15 IU is a conservative threshold for designation of immunity. Of 343 sera tested, only 1 false-positive was found by SRH with the 5 IU cutoff level. The SRH test could detect serum antibody levels as low as 2.5 IU, whereas 15 IU was generally the limit of resolution of the HI test. Data from sucrose density gradient fractionation of serum demonstrated that neither rubella-specific immunoglobulin M (IgM) nor early postinfection HI-reactive IgG was detected by SRH. However, diagnostic changes in antibody titer measured by SRH were in general greater than those measured by HI. The SRH test showed diagnostic titer changes in some sera containing specific IgM for which no such changes were detected by the HI test. A 2.5-mm difference in hemolytic zone diameters (a fourfold rise in international units) between acute- and convalescent-phase serum pairs was chosen as being of diagnostic significance. This difference was less than the minimum observed difference of 2.9 mm from 59 serum pairs showing diagnostic changes by HI and far exceeded (greater than 3.6 standard deviations) the within-test and individual variability seen for 95 pregnant women from whom samples were obtained during each trimester.     

A clinical trial with Alice/R-75 strain,live attenuated serum inhibitor-resistant intranasal bivalent influenza A/B vaccine

A clinical trial was conducted with Alice/R-75 strain live attenuated intranasal influenza A/B vaccine. With double blind control 88 adult volunteers were administered 2 doses of Alice/R-75 vaccine, 93 volunteers received one dose of Alice/R-75 vaccine and one dose placebo solution and 94 subjects were administered 2 doses of placebo solution. Twenty-three other subjects received Alice strain monovalent influenza A vaccine. For comparison, data from 21 subjects who received monovalent intranasal R-75 strain influenza B in two doses is included. The vaccine was generally well tolerated. Four-fold serum hemagglutination-inhibiting (HAI) antibody titer rises to A/England/42/72 occurred in 39% of the monovalent Alice strain vaccinees; in contrast 18% of those given 2 doses of bivalent Alice/R-75 vaccine and 11% of those given 1 dose of bivalent vaccine had similar four-fold HAI antibody titer rises. HAI antibody titer rises to influenza B/Hong Kong/72 occurred in 38% of R-75 strain monovalent vaccinees, 14% of Alice/R-75 2-dose vaccinees and 11% of Alice/R-75 one dose vaccinees. An epidemic of influenza at the onset of the study made evaluation of the efficacy of the vaccine impossible.This study was supported by a grant from Smith, Kline and French Laboratories, Philadelphia, Pennsylvania     

Comparison of hemagglutination inhibition assay, an ELISA-based micro-neutralization assay and colorimetric microneutralization assay to detect antibody responses to vaccination against influenza A H1N1 2009 virus

The hemagglutination inhibition (HI) assay has been the main method used to investigate immune responses to vaccination against influenza H1N1 (2009) virus. However microneutralization tests (MNT) have been shown to be more sensitive and more specific. In this study, the three methods of choice: (i) the HI assay, (ii) an ELISA-based conventional MNT and (iii) a colorimetric MNT in terms of their ability to detect antibody responses in serum pairs collected from 43 healthy individuals before and 21 days after vaccination were compared. The colorimetric MNT was established yielding intra- and inter-run imprecisions of 7.5% and 12.4%, respectively. Testing of antisera to seasonal influenza viruses demonstrated the assay to be specific for antibodies to influenza H1N1 (2009) virus. A good correlation between the three methods was found, being highest for the ELISA-MNT and the colorimetric MNT (r = 0.714 for geometric mean titers (GMT) and r = 0.695 for titer increases). Similar rates of fourfold titer increases were detected: 95.3% in the ELISA-MNT vs. 93.0% in colorimetric MNT and 95.3% in HI assay. The ELISA-based MNT demonstrated the highest titer range leading to the highest postvaccination GMT and the highest titer increase (>50-fold). The lowest GMTs were measured with the HI assay, while the colormetric MNT detected the highest GMT in prevaccination sera. Taken together, similar seroconversion rates were obtained with the three assays. The ELISA-MNT appeared to be the best method to compare absolute pre- and postvaccination GMTs. The colorimetric MNT, being less labour-intensive than the ELISA-MNT, seems to be a suitable tool in vaccination studies.     

Response of seronegative and seropositive adult volunteers to live attenuated cold-adapted reassortant influenza A virus vaccine.

The infectivity and immunogenicity of live attenuated A/Washington/897/80 cold-adapted reassortant virus vaccine was evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:4) and seropositive (hemagglutination inhibition titer, greater than 1:4) adult volunteers. The vaccine was efficient in infecting seronegative volunteers (94%). Moreover, 51% of seropositive vaccinees were infected by the virus. After live virus vaccination, greater than 83% of both seronegative and seropositive vaccinees achieved a level of nasal wash antibody previously associated with resistance to infection with influenza A virus. These findings indicate that both seronegative and seropositive vaccinees can benefit from live virus vaccination.     

Safety of and serum antibody response to cold-recombinant influenza A and inactivated trivalent influenza virus vaccines in older adults with chronic diseases.

Forty older adults with chronic diseases were vaccinated intranasally with either influenza A/California/10/78 (H1N1) (CR37) or influenza A/Washington/897/80 (H3N2) (CR48) virus. No clinically significant morbidity or decrement in pulmonary function occurred postvaccination. Two (15%) recipients of CR37 virus and twelve (44%) recipients of CR48 virus became infected with vaccine virus, as indicated by a fourfold rise in serum hemagglutination inhibition antibody titer; a fourfold rise in serum immunoglobulin G (IgG) or IgA antibody titer, indicated by enzyme-linked immunosorbent assay; isolation of vaccine virus from nasal washings; or all of these. Within 1 year after cold-recombinant vaccine virus vaccination, 18 vaccines received inactivated trivalent influenza virus vaccine parenterally. Of the vaccinees, 13 (72%) developed a fourfold rise in serum antibody titer to H1N1 antigen and 16 (89%) developed a fourfold rise in serum antibody titer to H3N2 antigen. We conclude that administration of these cold-recombinant vaccine viruses to older adults with chronic diseases was safe, but that serum antibody response rates were lower than those achieved with subsequently administered inactivated influenza virus vaccine given parenterally. However, the higher seroconversion rates attained by using the inactivated trivalent influenza virus vaccine do not necessarily mean that it is more efficacious in preventing infection or severe illness or both due to natural wild-type influenza A virus.     

Immunogenicity of the Trivalent Inactivated Influenza Vaccine in Young Children Less than 4 Years of Age,with a Focus on Age and Baseline Antibodies

In this study, we assessed the effects of the prevaccination titer and age on the immunogenicity of a low dose of influenza vaccine in children less than 4 years of age. A total of 259 children received two vaccine doses (0.1 ml for 0-year-olds and 0.2 ml for children 1 year of age or older) 4 weeks apart during the 2005/2006 season. The hemagglutination inhibition antibody titers were measured before vaccination and 4 weeks after the first and second doses. The geometric mean titer, mean fold rise, seroresponse proportion (≥4-fold rise in titer), and seroprotection proportion (titer ≥1:40) were calculated for the prevaccination titer and age categories. A multivariate logistic regression analysis was performed using the seroresponse and seroprotection proportions as dependent variables and the prevaccination titer and age as explanatory variables. As for the seroresponse against the H1 antigen after the first dose, the adjusted odds ratios of the prevaccination titers (versus <1:10) were 2.2 (95% confidence interval, 0.8 to 5.8) at 1:10 to 1:20 and 0.14 (0.04 to 0.49) at ≥1:40. The corresponding figures for ages were 0.03 (0.01 to 0.07) for the 0-year-olds and 0.17 (0.08 to 0.34) for the 1-year-olds compared with the 2- to 3-year-olds (P_trend < 0.001). Similar results were also obtained for the H3 and B strains. Significantly elevated odds ratios for seroprotection were observed with greater prevaccination titers and older ages for all strains. The prevaccination titer and age were independently associated with the antibody response in young children. The immune response was weaker in the younger children and those without preexisting immunity.     

Clinical and serologic effects of live attenuated serum inhibitor-resistant influenza B vaccine in seronegative adults.

The clinical effects, nasal and serum antibody responses, and virus excretion of a live attenuated serum inhibitor-resistant influenza B virus vaccine, R75, was evaluated in 43 seronegative healthy adults by a random double-blind study. Symptom responses were minimal and were not significantly different between vaccine and placebo groups. No fevers, abnormalities in physical examination or laboratory testing developed during 4 weeks of observation. Among vaccinees, 10 (48%) developed serum hemagglutination-inhibition (HI) antibodies, 16 (76%) developed serum neutralization (N) antibodies and 4 (19%) developed nasal N antibodies. The GMT responses from study day 0 to day 28 were 4.0 to 10.4 for serum HI, 1.8 to 9.8 for serum N, and 1.0 to 1.4 for nasal N. There were no significant titer changes in the placebo group. No virus excretion was detected. Although there are some questions concerning the relationship of antibody levels to protection, the low antibody responses in this study are an indication that R75 is not sufficiently immunogenic.     

Diagnosis of Mycoplasma pneumoniae pneumonia: sensitivities and specificities of serology with lipid antigen and isolation of the organism on soy peptone medium for identification of infections.

The sensitivities and specificities of isolation and serology for detection of Mycoplasma pneumoniae infections were determined for 3,546 pneumonia patients for whom both isolation and serological data were available. Soy peptone, fresh yeast extract, horse serum-supplemented agar, and diphasic medium were employed for isolation, and the lipid antigen of M. pneumoniae was used for serodiagnosis by complement fixation. The number of M. pneumoniae colonies most frequently detected was 200 to 600 per throat swab, with a range of less than or equal to 60 to greater than or equal to 2,000. The use of diphasic medium increased the number of isolates by 26% compared with direct isolation on agar plates. The organism was isolated from 360 of 525 patients who showed fourfold or greater antibody increases in their paired sera, resulting in a sensitivity of culture of 68%. When persons with titers of greater than or equal to 32 but no fourfold increase were used as the reference, the sensitivity of culture was 58%. The combined sensitivity of the culture method for persons with serological evidence of infection (fourfold increase and titer of greater than or equal to 32) was 64%. The specificity of the culture method was 97% for the 2,527 serologically negative persons. Fourfold antibody increases were found in 360 of 674 persons with isolates of the organism, resulting in a sensitivity of 53%. An additional 247 persons showed titers of greater than or equal to 32 (without a fourfold increase), resulting in a combined sensitivity of 90% for serology with the lipid antigen for the detection of antibodies in culture-positive persons. Fourfold antibody increases were found in 6% of culture-negative persons, resulting in a specificity of 94%. The quantitative culture results provide important base-line data for the development of rapid diagnostic tests for M. pneumoniae infection.     

Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: reevaluation of correlates of protection

The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the "gold standard" correlate of protection for meningococcal C disease is a titer of > or =4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of > or =8 showed that for 93% (27 of 29) the titer was > or =4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or > or =128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of > or =128 had hSBA titers of > or =4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of > or =4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result > or =4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of > or =128 after a 10-microg polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-microg dose. Furthermore, the increase in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.     

Antibody reactive in antibody-dependent cell-mediated cytotoxicity following influenza virus vaccination

The antibody reactive in antibody-dependent, cell-mediated cytotoxicity (ADCC) to influenza virus-infected cells was measured in two groups of seven volunteers each, before and after immunization with inactivated or live attenuated A/Victoria/3/75 influenza virus vaccines. Age-matched controls were seven adult individuals who experienced natural influenza infection due to A/Victoria/3/75-like virus strain. After inactivated whole influenza virus immunization all the subjects showed a significant rise of the antibody reactive in ADCC (from a mean value of 4.7% to 17.1% cytotoxicity, before and 5 weeks after immunization, respectively) as well as of hemagglutination inhibition (HI) antibody (fourfold or greater increase). These immune responses were similar to those observed among naturally infected controls. After live attenuated virus vaccination, no significant increase in titer of antibody reactive in ADCC was detected, even though the vaccine induced significant increase of HI antibody titer. Little correlation was found between ADCC and HI antibody rises in sera of recipients of inactivated virus vaccine and of naturally infected individuals, while, in live attenuated influenza virus vaccinees, the rise of HI antibody titer did not correspond to a significant increase of ADCC antibody titer; several subjects who developed a significant rise in ADCC antibody titer did not show significant variation in antibody to neuraminidase and/or to complement fixation influenza virus antigens.     

Immunization with a Pseudomonas aeruginosa immunotype 5 O polysaccharide-toxin A conjugate vaccine: effect of a booster dose on antibody levels in humans.

Healthy adult volunteers were vaccinated on day 0 and 28 and at 15 months with a Pseudomonas aeruginosa immunotype 5 O polysaccharide-toxin A conjugate vaccine. Immunization resulted in mild, transient local reactions in less than 20% of the subjects. Maximal immunoglobulin G (IgG) antibody titers to both toxin A and lipopolysaccharide (LPS) as determined by enzyme-linked immunosorbent assay were seen at day 42, at which time 50% of the vaccinees showed a fourfold or greater rise in toxin A-neutralizing titers. By 15 months postvaccination, both antitoxin A and anti-LPS IgG antibodies had markedly declined. A booster dose of vaccine administered at 15 months evoked a vigorous anti-toxin A IgG antibody response with 100% of the volunteers showing a fourfold or greater rise in neutralizing antibody titer compared with preimmunization levels. In contrast, there was no significant elevation of anti-LPS IgG antibody levels. At 24 months postimmunization, only anti-toxin A antibody levels were significantly higher than preimmunization levels.     

Clinical and serologic effects of Alice strain live attenuated influenza A (H3N2) virus vaccine in an adult population

Alice strain live attenuated influenza A (H3N2) virus was evaluated in prison volunteers. By random double blind allocation, 94 volunteers received Alice strain vaccine (AS) intranasally and 97 received placebo. The vaccine was well tolerated, and there was no serious morbidity. The number, type, duration, and severity of symptoms was not significantly different between the vaccine and placebo groups. Seventy-five per cent of vaccines with initial HAI titers less than or equal to 1:8 had 4 fold or greater titer responses on day 30. Placebo recipients experienced no titer changes. The GMT among vaccinees increased from 23.5 prior to vaccination 59.7 30 days later. Surveillance activities failed to document influenza A (H3N2) infection in the volunteer population during a 6 month follow-up period. Additional studies on the protective effects of the vaccine are required before efficacy can be determined.     

Significance of specific Epstein-Barr virus IgA and elevated IgG antibodies to viral capsid antigens in nasopharyngeal carcinoma patients

The feasibility of using elevated Epstein-Barr virus (EBV) specific-IgG antiviral capsid antigen (VCA) and IgA anti-VCA antibody levels as an aid in diagnosis of nasopharyngeal carcinoma (NPC) was analyzed by determination of serum antibody titers to EBV in 54 NPC patients, 114 healthy blood donors, and 40 family members by the immunoperoxidase assay (IPA). No significant difference was found in the prevalence rate of EBV IgG anti-VCA antibodies (titer greater than or equal to 20) between the patient group and the control and family groups (100% vs 92% and 90%, respectively). The prevalence rate of elevated EBV IgG anti-VCA titers (greater than or equal to 80, greater than or equal to 160, greater than or equal to 320, greater than or equal to 640) was significantly higher in the NPC patients than in controls. For example, at an IgG titer of greater than or equal to 320, the prevalence rate was 82% in the NPC patient group and 1.7% in the controls (P less than 0.0001). The prevalence of EBV IgA anti-VCA antibodies (greater than or equal to 10) was significantly higher in the NPC patients than in control and family groups (82% vs 6.1% and 0%, respectively). The prevalence rate for elevated EBV IgA anti-VCA (greater than or equal to 20) was found to be significantly higher (P less than 0.0001) in NPC patients than in the control group (70% vs. 1.7%). A significantly high proportion (P = 0.0004) of NPC patients who had serum EBV IgA anti-VCA titers of less than 20 had elevated IgG titers to VCA greater than or equal to 320 (21% vs 1.7% among controls). It appears that testing for IgG antibodies at a serum dilution of 1:320 and for IgA antibodies at a dilution of 1:20 by the IPA technique comprises the best combination for the differentiation between NPC patients and health controls (91% vs 3.4%), and it is suggested that these be used as screening markers for NPC patients.     

Clinical trial with "R-75" strain live, attenuated, serum inhibitor-resistant intranasal influenza B vaccine.

The "R-75" strain live, attenuated, serum inhibitor-resistant influenza B vaccine was administered intranasally by drops in two doses 14 days apart to 21 volunteers. Each vaccinee was paired with a close associate (roommate or workmate) who similarly received two doses of a placebo solution. Although about 50% of both vaccine and placebo recipients complained of symptoms after dosage, the severity of symptoms was greater in vaccine recipients. Fourfold serum hemagglutination-inhibiting antibody titer rises occurred in 38% of vaccine recipients, and four vaccines had fourfold titer rises of nasal hemagglutination-inhibiting antibody. Vaccine virus was isolated from three asymptomatic vaccine recipients. There was no virological or serological evidence of the vaccine virus spreading to placebo recipients.