Hemagglutination Inhibition Antibody Levels Research Articles

Influenza Outbreaks in Nursing Homes: How Effective Is Influenza Vaccine in the Institutionalized Elderly?

During the 1984-1985 influenza season, outbreaks of influenza A (H3N2) occurred in three Connecticut nursing homes. Influenza vaccination rates were 67% (96 out of 144), 35% (30 out of 85) and 69% (332 out of 483), respectively. The relative risk of illness for vaccinated compared to unvaccinated residents was 1.8 (95% confidence interval, 0.6, 5.9), 1.6 (95% confidence interval, 0.8, 3.0) and 1.1 (95% confidence interval, 0.8, 1.7) for each of the three nursing homes, respectively. In the third outbreak, 22 vaccinated residents without clinical illness had a geometric mean titer of hemagglutination-inhibition (HI) antibody of 20. Although low, this titer was significantly higher than that of nine unvaccinated residents without clinical illness (12, p less than .05); only three (14%) vaccinated residents had HI titers of greater than or equal to 40. These results suggest that levels of HI antibody in vaccinated residents were not protective at the time of the third outbreak, four to five months after vaccination. In general, the study of vaccine effectiveness in nursing homes is limited by sample size and statistical power. Despite these limits, the retrospective investigation of influenza outbreaks in nursing homes is often the only practical way to evaluate influenza vaccine effectiveness in the elderly on a yearly basis.

Antibody responses of humans and nonhuman primates to individual antigenic sites of the hemagglutinin-neuraminidase and fusion glycoproteins after primary infection or reinfection with parainfluenza type 3 virus

An unusual feature of human parainfluenza virus type 3 (PIV3) is ita ability to cause reinfection with high efficiency. The antibody responses of 45 humans and 9 rhesus monkeys to primary infection or subsequent reinfection with PIV3 were examined to identify deficiencies in host immunologic responses that might contribute to the ability of the virus to cause reinfection with high frequency. Antibody responses in serum were tested by using neutralization and hemagglutination inhibition (HI) assays and a monoclonal antibody blocking immunoassay able to detect antibodies to epitopes within six antigenic sites on the PIV3 hemagglutinin-neuraminidase (HN) glycoprotein and eight antigenic sites on the fusion (F) protein. Primary infection of seronegative infants or children with PIV3 stimulated strong and rather uniform HI and neutralizing antibody responses. More than 90% of the individuals developed antibodies to four of the six HN antigenic sites (including three of the four neutralization sites), but the responses to F antigenic sites were of lesser magnitude and varied considerably from person to person. Young infants who possessed maternally derived antibodies in their sera developed lower levels and less frequent HI, neutralizing, and antigenic site-specific responses to the HN and F glycoproteins than did seronegative infants and children. In contrast, children reinfected with PIV3 developed even higher HI and neutralizing antibody responses than those observed during primary infection. Reinfection broadened the HN and F antigenic site-specific responses, but the latter remained relatively restricted. Adults possessed lower levels of HI, neutralizing, and antigenic site-specific antibodies in their sera than did children who had been reinfected, suggesting that these antibodies decay with time. Rhesus monkeys developed more vigorous primary and secondary antibody responses than did humans, but even in these highly responsive animals, response to the F glycoprotein was relatively restricted following primary infection. Bovine PIV3 induced a broader response to human PIV3 in monkeys than was anticipated on the basis of their known relatedness as defined by using monoclonal antibodies to human PIV3. These observations suggest that the restricted antibody responses to multiple antigenic sites on the F glycoprotein in young seronegative infants and children and the decreased responses to both the F and HN glycoproteins in young infants and children with maternally derived antibodies may play a role in the susceptibility of human infants and young children to reinfection with PIV3.

Japanese encephalitis virus infection in cattle: Changes in antibody distribution in the central district of Japan during a 4-year period

During 4 years from 1982 to the end of 1985, serum samples were collected from a total of 1970 cattle in summer. They were investigated for the level of hemagglutination-inhibition antibody against Japanese encephalitis virus. The antibody-positive rate in each year ranged from 59.4 to 85.9% (the mean rate of 4 years: 68.3%), and antibody titers were distributed from 1:10 to 1:320. The results indicate that meteorological factors affecting the generation of the vector mosquitos, especially mean atmospheric temperature and total rainfall in June, indirectly caused changes in the antibody-positive rate in each year.

Infectious bronchitis in laying hens: The relationship between haemagglutination inhibition antibody levels and resistance to experimental challenge

In three separate and unrelated experiments, in which vaccinated hens were challenged with virulent infectious bronchitis virus, the ability of individual hens to maintain egg production was related to their serum haemagglutination inhibition antibody titre at the time of challenge. It was found that, regardless of the vaccination programme used, the ability of laying hens to withstand infectious bronchitis virus challenge, as measured by the effect upon their egg production, is directly related to individual antibody titre at the time of challenge. In all three experiments, birds with antibody titres of >/=8 Iog2 (n = 82) did not show a significant reduction in egg production after challenge while those with titres within the range 5-7 log(2) inclusive (n = 126), over a period of 3 or 4 weeks after challenge, showed a significant reduction in their rate of egg lay, viz: 0.38, 0.33 and 0.47 eggs per hen per week, respectively and those with titres <4 log(2) (n = 101) showed, over the same time period, a reduction of 1.0, 0.45 and 1.16 eggs per hen per week, respectively. The ability of different vaccination programmes to stimulate uniformly high antibody responses to infectious bronchitis virus, and hence good overall protection of egg production was compared. It is concluded that the programme of choice is first to vaccinate the birds with a highly attenuated strain of live infectious bronchitis vaccine during rearing (H120), followed by the injection of a potent killed oil emulsion adjuvant vaccine at point-of-lay. The ability of the less attenuated H52 strain of live infectious bronchitis vaccine to interfere with response to killed vaccine was demonstrated in two of the three experiments. In both cases this interference was accompanied by an increased susceptibility of the hens to the effect of infectious bronchitis virus challenge on egg production.

Maternally-derived antibodies to porcine parvovirus and their effect on active antibody production after vaccination with an inactivated oil-emulsion vaccine.

Two sows which had been vaccinated with an oil-emulsion porcine parvovirus vaccine, and had developed high haemagglutination-inhibiting antibody levels to the virus, farrowed three successive litters each, a total of 74 piglets. Serum samples from these piglets were tested for haemagglutination-inhibiting antibody at birth, three and 17 days after birth, and at monthly intervals thereafter to study the decline of maternally-derived antibody. Regression curves were constructed from the data to show the projected pathway (mean and 95 per cent tolerance limits) of the decline of maternally-derived antibody. Approximately half the pigs still had positive titres of up to 1/160 at six months old, and traces of antibody were detected in a few pigs at nine months. Thus, even at the onset of breeding some gilts can have maternally-derived antibody which may interfere with their ability to develop active immunity to porcine parvovirus. From the same litters three groups of 12 pigs were selected randomly and were vaccinated with a single dose of the oil-emulsion vaccine at 70 days, 130 days or 190 days respectively. Despite the presence of moderate to high titres of maternally-derived antibody, especially in the younger pigs, all of those vaccinated showed strong and long lasting antibody responses to the vaccine. High serum antibody titres at the time of vaccination seemed to depress the response to the vaccine slightly but the effect was not statistically significant. These results have important implications for prevention of reproductive failure induced by porcine parvovirus.

Comparison of Egg Yolk and Serum for the Detection of Mycoplasma gallisepticum and M. synoviae Antibodies by Enzyme-Linked Immunosorbent Assay

Egg yolk was evaluated in the enzyme-linked immunosorbent assay (ELISA) as an alternative source of antibodies for detection of Mycoplasma gallisepticum (MG) and M. synoviae (MS) infections in chickens. There was no statistically significant difference (P greater than 0.05) between the ELISA geometric mean titers (GMTs) of saline-diluted egg yolk and chloroform-extracted egg yolk, and both preparations had a high correlation coefficient (0.87 for MG; 0.97 for MS). The saline-diluted and chloroform-extracted yolk had a relative sensitivity of 90% and specificity of 98% in the MG ELISA; in MS ELISA they were 100% and 96%, respectively. Hemagglutination-inhibition (HI) results with chloroform-extracted samples were satisfactory, but those with saline-diluted samples were not. Neither preparation was satisfactory for use in the rapid plate agglutination (RPA) test. A 1-ml sample of yolk was compared with the whole-yolk method. The chloroform-extracted whole yolk yielded a significantly higher (P less than 0.05) GMT in the MG ELISA; however, there was no statistically significant difference (P greater than 0.05) between GMTs yielded by the two procedures in the MS ELISA. The correlation coefficients for the two sampling methods were 0.73 for MG ELISA and 0.63 for MS ELISA. ELISA detected no statistically significant difference (P greater than 0.05) between GMTs of serum and chloroform-extracted yolk from individual birds. Results with the HI test were comparable to those with ELISA on the same samples. The RPA test yielded comparable results on the serum samples. No statistically significant differences (P greater than 0.05) were observed in HI or ELISA antibody levels between egg-yolk samples and sera on random samples collected from nine flocks that were MG- and MS-free or were infected with MG, MS, or both; however, egg-yolk samples tended to have slightly higher titers than sera in both tests. The optimum screening dilution of chloroform-extracted yolk for detecting MG and MS antibodies by ELISA was 1:800.

Immune response of adults to sequential influenza vaccination.

Annual immunization against influenza is recommended for numerous individuals, but the antibody response to sequential vaccination has not been well characterized. Levels of hemagglutination-inhibition antibody were measured in adults given either two or three doses of trivalent influenza vaccine at six-month intervals. A significant rise in the number of individuals with antibody titers of greater than or equal to 40 was seen for all three antigens only after initial vaccination. Repeated vaccination was necessary to maintain adequate antibody levels only to the A/Brazil (H1N1) antigen; it did not significantly affect the proportions of individuals with protective levels of antibody to either the A/Bangkok (H3N2) or the B/Singapore 222/79 antigens. These findings do not support the current recommendation for annual immunization when the vaccine formulation has not changed.

Disease due to cytomegalovirus and its long-term consequences in renal transplant recipients. Correlation of allograft survival with disease due to cytomegalovirus and rubella antibody level

We prospectively studied 52 consecutive renal allograft recipients who retained their grafts at least three months. The transplant recipients were observed for five years or longer. Disease due to cytomegalovirus (CMV) occurred in nine (17.3%). Manifestations of disease due to CMV that were significantly more common than in chronologically matched controls in comparable periods after transplantation included fever, leukopenia, hepatic function abnormalities, pneumonia, and renal dysfunction. Life-table analyses suggested a trend of decreased allograft survival with disease due to CMV, but the difference between controls was not statistically significant. A significant inverse correlation were noted between the level of hemagglutination inhibition antibody to rubella virus reached after transplantation and allograft survival. This correlation remained statistically significant even when patients with disease due to CMV were excluded from the analysis.

Disease due to Cytomegalovirus and Its Long-term Consequences in Renal Transplant Recipients

• We prospectively studied 52 consecutive renal allograft recipients who retained their grafts at least three months. The transplant recipients were observed for five years or longer. Disease due to cytomegalovirus (CMV) occurred in nine (17.3%). Manifestations of disease due to CMV that were significantly more common than in chronologically matched controls in comparable periods after transplantation included fever, leukopenia, hepatic function abnormalities, pneumonia, and renal dysfunction. Life-table analyses suggested a trend of decreased allograft survival with disease due to CMV, but the difference between controls was not statistically significant. A significant inverse correlation were noted between the level of hemagglutination inhibition antibody to rubella virus reached after transplantation and allograft survival. This correlation remained statistically significant even when patients with disease due to CMV were excluded from the analysis. (<i>Arch Intern Med</i>1983;143:1126-1129)

Oncogenity of BK virus for immunosuppressed hamsters.

Tumors were induced by BK virus (BKV) inoculated intravenously in 3-week-old Syrian golden hamsters immunosuppressed with anti-lymphocyte serum or methylprednisolone acetate alone or in association with gamma-radiation (60Co). The induced neoplasms were ependymoma, carcinoma of pancreatic islets, lymphoma, osteosarcoma, undifferentiated sarcoma, kidney and renal pelvis carcinoma, pheochromocytoma and hemangiosarcoma. High levels of insulin and glucagon and altered concentrations of glucose were detected in blood of animals with tumors of pancreatic islets. No antibodies to BKV tumor antigen (TAg) and low levels of hemagglutination-inhibition antibodies to BKV viral coat protein Ag were detected in hamster sera. BKV TAg was found in tumors by complement fixation. Blot hybridization analysis of tumor DNA showed the presence of both free and integrated BKV genomes in tumor cells. BKV DNA inoculated intravenously and subcutaneously in immunosuppressed or immunocompetent hamsters was not oncogenic, whereas it was weakly oncogenic when inoculated intracerebrally.

PREVALENCE OF HEMAGGLUTINATION INHIBITION ANTIBODY TO CURRENT STRAINS OF THE H3N2 AND H1N1 SUBTYPES OF INFLUENZA A VIRUS IN SERA COLLECTED FROM THE ELDERLY IN 1976

Sera were collected in 1976 from 182 individuals born between 1876-1935, who included patients in a large local nursing home in Orange County, California, and patients and staff at the University of California, Irvine Medical Center. Sera were treated with receptor-destroying enzyme and assayed for hemagglutination inhibition (HI) antibody to recent strains of influenza A virus. The antigens tested were: A/Victoria/3/76 and A/Texas/1/77 for subtype H3N2; A/New Jersey/8/76, A/X53 and A/Swine/1976 for the A/swine influenza virus-like strains of subtype H1N1; and A/Brazil/11/78, A/Fort Monmouth/1/47 and A/Francis Warren/1/50 for the A/Fort Monmouth/47 virus-like strains of subtype H1N1. For individuals grouped by five- and 10-year intervals of the year of birth, the geometric mean and standard error for HI antibody to each antigen were calculated and plotted vs. date of birth. The results indicate that for a majority of individuals born between 1876-1900, the level of HI antibody would be protective against H3N2 but not against the strains of H1N1. In addition, a majority of individuals born between 1900-1925 had levels of antibody that should be protective against both H3N2 and the A/swine influenza virus-like strains of H1N1 but not against the A/Fort Monmouth/47 virus-like strains of H1N1. These findings could be important when deciding on the antigenic composition of vaccines to be used in those age groups that are most vulnerable to the complications of influenza. In addition, data were obtained that suggest that the A/Fort Monmouth/47 virus-like strains of H1N1 recycle in 35-40 years rather than in 65-70 years as has been demonstrated previously for H2N2 and H3N2.

Rubella Antibody Persistence After Immunization

A comparative field trial of three live, attenuated rubella virus vaccines (Cendehill, HPV 77 DE-5, and HPV-77 DK-12) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Following initial seroconversion rates of more than 98%, periodic serological testing of the study population was conducted to assess the durability of vaccine-induced immunity. In February 1980, ten years after the initiation of the study, 741 of the 5,153 original susceptible vaccinees were still enrolled in the study. After a drop of approximately 50% in mean hemagglutination-inhibition (HI) titer for each of the vaccine groups during the first four years following vaccination, the HI titer levels for all three groups have been generally stable between years 4 and 10. The frequency of reversion to an HI titer of less than 10 has remained less than 0.5% per year. A measurable HI antibody level has persisted in more than 97% of all vaccines over the ten-year period. This study indicates that when potent rubella vaccine is administered properly, a high seroconversion rate and a high rate of antibody persistence should be expected.

THE RESPONSE OF AUSTRALIAN CHICKENS NATURALLY INFECTED WITH AVIRULENT NEWCASTLE DISEASE VIRUS TO CHALLENGE WITH VELOGENIC NEWCASTLE DISEASE VIRUS

SUMMARY Sixty‐eight breeder chickens, 4 to 12 months of age, were taken from Australian flocks that had been naturally infected with avirulent Newcastle disease virus (NDV) and transported by air to Malaysia. Nearly all the breeders had haemagglutination inhibition antibodies to NDV, at titres of from 2 to 128. Thirty‐two were inoculated intranasally with an Asian, velogenic, viscerotropic strain of NDV and all survived this challenge. Thirty‐six were exposed to contact infection with the same velogenic NDV and 2 died of Newcastle disease within 14 days. The levels of haemagglutination inhibition antibodies against NDV increased in the surviving breeders after challenge, reaching 2048 or greater in a few birds. Velogenic NDV was isolated from a cloacal swab from one clinically normal breeder 10 days after challenge by contact. Cloacal swabs taken 7 to 10 days after challenge from another 23 breeders yielded no NDV.Twenty‐four broilers, 7 weeks of age, were also transported from Australia to Malaysia. All lacked detectable haemagglutination inhibition antibody to NDV and they were from a flock with no detectable antibody to NDV. Twelve were challenged with velogenic NDV intranasally and 12 were subjected to contact challenge. All broilers died of Newcastle disease within 13 days.

Human antibody to influenza C virus: its age-related distribution and distinction from receptor analogs.

Sera from persons of four age groups (1 to 2 years, 2 to 5 years, 20 to 30 years, and 65 to 85 years) were analyzed for hemagglutination inhibition (HI) activity for influenza C virus. Significant HI activity was found in 66% of the 237 sera tested, and titers ranged from 8 to 512. In the yoiung adult group, 96% had antibody and the highest mean titer (74.7) of any age group. Positive sera were far less common in young children (36 to 47%), and relatively low titers (18.3) were common among adults over 65. The high percentage of sera with antibody to influenza C virus suggests that infections with this virus occur at a rate greater than previously recognized. The high percentage of young adults with elevated levels of HI antibody suggested either that an immune response to influenza C infections is common or that the observed HI activity might be attributable, in part at least, to nonspecific inhibitors in the sera. We showed both directly and indirectly that most if not all the inhibitory activity in the human sera we examined was due to specific antibody, mostly immunoglobulin G. This conclusion is based on the finding that the single serum protein fraction with HI activity was found to have a molecular weight equivalent to that of 7S antibody (150,000) and that the HI activity was removed by absorption to staphyloccal protein A. Moreover, immunoglobulin from only HI-positive sera bound specifically to cells infected with influenza C virus, as shown by inhibition of hemadsorption and immunofluorescence. These findings were supported by similar results obtained with chicken antisera to C virus.

Protection of laying hens against infectious bronchitis with inactivated emulsion vaccines.

Commercially-reared laying chickens were challenged at 31 weeks of age with a virulent infectious bronchitis (IB) virus. They showed a sharp drop in egg production, despite having been vaccinated at four and eight weeks old with live attenuated IB vaccines to a recommended schedule. In contrast, similar birds that had been further immunised at point-of-lay with inactivated oil emulsion IB vaccine, or with a combined IB/Newcastle disease (ND) emulsion vaccine, showed no detectable fall in egg production after the same challenge. Unvaccinated susceptible specific pathogen-free birds challenged at the same time stopped laying almost completely. In the birds revaccinated with emulsion vaccine, measurement of haemagglutination inhibition antibody levels to IB showed their geometric mean titres to be raised from less than 5 log2 at the time of vaccination to over 10 log2 four weeks later. Their antibody levels did not rise further followining the IB challenge whereas in the birds that had not been revaccinated antibody rises to nearly 10 log2 were detected after the same challenge. For pullets vaccinated earlier with live IB vaccine, revaccination with inactivated IB or IB/ND oil emulsion vaccine at point-of-lay provides a safe and effective way of protecting their egg production against IB infection.

Susceptibility of the horse to experimental inoculation with louping ill virus

A group of ponies was inoculated with an equine strain of louping ill (LI) virus either subcutaneously or by a combination of the intravenous and subcutaneous routes. All the susceptible ponies were febrile for 3 to 4 days after inoculation. No gross behavioural changes were observed in any animal. Every pony was viraemic for 6 to 7 days after inoculation, with maximal titres of virus present on days 1 to 3. Decline and cessation of viraemia was associated with the appearance and rapid increase in the titres of circulating haemagglutination-inhibiting (HI), complement-fixing (CF) and serum neutralizing (SN) antibodies. The pattern of development of these antibodies was broadly similar, with SN antibodies detectable 1 to 2 days before HI or CF responses. Formation of precipitating antibodies was irregular with two ponies remaining seronegative. The HI antibody titres were lower and less persistent than corresponding CF and SN titres. Three months after primary inoculation, each pony was reinoculated either subcutaneously or intravenously with LI virus. Although the rise in HI antibody levels was small, titres persisted longer than after primary virus inoculation. With the exception of precipitating antibodies, the patterns of the secondary CF and SN responses were broadly similar to their respective primary profiles. Neither the viraemia which developed nor the primary or anamnestic antibody response varied appreciably with virus dose or route of inoculation. The results of this study confirm the susceptibility of the horse to LI virus. Moreover, most of the ponies developed viraemia of sufficient intensity for 2 to 3 days after challenge potentially to infect Ixodes ricinus nymphs. It is suggested that the horse might be considered a possible amplifying host of LI virus.

Neutralization test in influenza: use in individuals without hemagglutination inhibition antibody.

In influenza immunization trials, patients who were seronegative by the hemagglutination inhibition test could be divided into two groups according to preimmunization levels of neutralizing (Neut) and neuraminidase inhibition (NI) antibodies. The group with low levels of Neut and NI antibodies usually developed adequate levels of hemagglutination inhibition antibody after one dose of vaccine, and the group with undetectable Neut and NI antibodies did not.

A contribution of cellular immunity to protection against influenza in man.

The degree of lymphocyte transformations and leukocyte migration inhibition (LMI) in the presence of inactivated A/Scotland/74 (H3N2) influenza virus vaccine was measured in blood samples collected from 56 medical student volunteers. At the same time the volunteers were skin tested, using the same vaccine. Using the antigenically similar WRL 105 (H3N2), recombinant influenza virus, the level of haemagglutination-inhibiting (HI) antibodies in serum, and neutralizing antibodies in nasal washings collected from the volunteers, were also determined. Each volunteer was then inoculated with live, attenuated WRL 105 influenza virus vaccine and infections demonstrated by virus isolations and serology. Correlations between the ability to infect the volunteers and the various parameters of humoral and cellular immunity were then determined. The results showed a good correlation between the level of serum HI antibody and infection. Thus 16 of 20 volunteers with serum HI antibody titres of 1:10, but only 6 of 20 volunteers with antibody levels of 1:30, showed evidence of infection. No direct correlation was observed between any of the other parameters measured and infection by WRL 105 virus. However, when the LMI and serum HI antibody levels were considered together, a contribution of cellular immunity, as measured by the LMI test, could be found. Of 19 volunteers with low serum HI antibody and low LMI levels, 16 were infected, whereas of 13 volunteers with low HI antibody, but with high LMI levels, only 6 showed evidence of infection with WRL 105 influenza virus.

Screening and Immunization of Rubella-Susceptible Women

Four hundred and fifty childbearing-aged women were screened for rubella hemagglutination inhibition (HI) antibody after a clinical history of susceptibility was obtained. One hundred and forty-nine (33%) were found to be susceptible (titers less than 1:8), pointing out the need for a move active immunization program for susceptible young women and for routine vaccination of children. Clinical history correlated poorly with the level of HI antibody. One hundred percent of the patients were vaccinated and protective antibody titres developed in 97%. Since titers are higher after infection than after vaccination, periodic reevaluation of the vaccinated group may be indicated if immunity is to be ensured.

Evaluation of Wistar RA27/3 Rubella Virus Vaccine in Children

Because the Wistar RA27/3 strain rubella virus vaccine has potentially important advantages over rubella vaccines currently licensed in the United States, a field trial was conducted in Minnesota and Wisconsin in 1974 to evaluate RA27/3 in this country. Two hundred eighty-five (99.7%) of 286 susceptible children given RA27/3 subcutaneously seroconverted, with a geometric mean hemagglutination inhibition (HI) titer of 81.2. Twenty-eight (23%) of 122 children with rubella antibodies before immunization had fourfold or greater rises in rubella HI titers. The highest percentage of booster responses occurred in children with low preimmunization titers. Side effects were reported in 34% of subjects, but only one reaction associated with RA27/3 was serious: in a 5-year-old boy, arthritis of the left hip developed 31 days after immunization. This study indicates that RA27/3 vaccine produced a very high rate of seroconversion with high postimmunization HI titers. The ability to elicit significant booster responses in children with low levels of HI antibodies suggests that RA27/3 could be used to boost immunity in women of childbearing age whose rubella titers have declined to undetectable levels.