An economic analysis of the current universal 2-dose measles-mumps-rubella vaccination program in the United States

To evaluate the economic impact of the current 2-dose measles-mumps-rubella (MMR) vaccination program in the United States, a decision tree-based analysis was conducted with population-based vaccination coverage and disease incidence data. All costs were estimated for a hypothetical US birth cohort of 3803295 infants born in 2001. The 2-dose MMR vaccination program was cost-saving from both the direct cost and societal perspectives compared with the absence of MMR vaccination, with net savings (net present value) from the direct cost and societal perspectives of US dollars 3.5 billion and US dollars 7.6 billion, respectively. The direct and societal benefit-cost ratios for the MMR vaccination program were 14.2 and 26.0. Analysis of the incremental benefit-cost of the second dose showed that direct and societal benefit-cost ratios were 0.31 and 0.49, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector had little effect on the results. From both perspectives under even the most conservative assumptions, the national 2-dose MMR vaccination program is highly cost-beneficial and results in substantial cost savings.     

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

Introduction

Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response.

Humoral and cell-mediated immune responses in children and adults after 1 and 2 doses of varicella vaccine

Humoral and cell-mediated immune responses to varicella-zoster virus (VZV) have been evaluated after 1 and 2 doses of live attenuated varicella vaccine, Oka strain, in several studies. One dose of varicella vaccine, however, elicits detectable immune responses that are low and, in some cases, may be insufficient for complete protection against the virus after the normal decline in humoral and cell-mediated immunity with time. In contrast, immune responses after 2 doses are significantly higher and approximate the levels seen after natural disease. These investigations of vaccine-induced immunity suggest that 2 doses of VZV vaccine will better achieve the goals of the VZV vaccination program, by reducing the VZV burden of disease in childhood and preventing accumulation of young adults who are susceptible to or only partially protected from varicella.     

Evaluation of the immune response to a 2-dose measles vaccination schedule administered at 6 and 9 months of age to HIV-infected and HIV-uninfected children in Malawi

BACKGROUND: The World Health Organization recommends that infants at high risk for developing measles before 9 months of age, including human immunodeficiency virus (HIV)-infected infants, receive measles vaccination (MV) at 6 and 9 months of age. METHODS: Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to receive MV at 6 and 9 months, MV at 9 months, or routine MV without follow-up. Blood samples were obtained before and 3 months after each MV. Data were collected on adverse events for 21 days after each MV, at all clinic visits, on any hospitalization, and for subjects who died. HIV-infection status was determined by antibody assays and polymerase chain reaction; the presence of measles IgG was determined by EIA. RESULTS: Twenty-two hundred mother-infant pairs were enrolled. After the first and second doses of measles vaccine, respectively, the percentages of children who were measles seropositive were 59% (36 of 61) and 64% (29 of 45) among HIV-infected children, 68% (152 of 223) and 94% (189 of 202) among HIV-exposed but uninfected children, and 62% (288 of 467) and 92% (385 of 417) among HIV-unexposed children. Of 521 HIV-unexposed children vaccinated only at 9 months, 398 (76%) were measles seropositive at 12 months. No serious vaccine-related adverse events were identified. CONCLUSIONS: An early, 2-dose MV schedule was immunogenic, but a higher proportion of HIV-infected children remained susceptible to measles, compared with HIV-uninfected children (whether HIV exposed or HIV unexposed).     

Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination

BACKGROUND: Postexposure vaccination strategies rely on a rapid induction of poxvirus-specific immune responses. Postvaccination cell-mediated immune (CMI) responses have not been compared by use of controlled trials in previously vaccinated (vaccinia-nonnaive) and nonvaccinated (vaccinia-naive) individuals. METHODS: To assess the time course of vaccinia-specific CMI responses, 20 previously vaccinated and 10 vaccinia-naive individuals were vaccinated with Dryvax, and serial blood samples were drawn. RESULTS: Both groups developed peak levels of vaccinia-specific interferon (IFN)- gamma -producing T cells by day 14 after vaccination. In vaccinia-nonnaive individuals, vaccinia-specific CMI responses were detected by day 7 after vaccination and preceded the increase in antibody titers. IFN- gamma enzyme-linked immunospot responses were significantly different between the 2 groups on days 7 (greater in vaccinia-nonnaive than in vaccinia-naive individuals) and 14 (greater in vaccinia-naive than in vaccinia-nonnaive individuals). Lymphoproliferation responses in vaccinia-nonnaive individuals were significantly higher on days 3 and 7, but cytotoxic T cell lysis activity was not statistically different at any time point. Antibody responses conformed to expected primary and secondary patterns of induction. CONCLUSIONS: This study demonstrates that the kinetics of CMI responses are different after primary vaccination versus after revaccination and indicates that memory can exist in individuals vaccinated >/=30 years ago. These data support the epidemiological observation in smallpox outbreaks that successful revaccination within 4 days of exposure is partially protective. In vaccinia-nonnaive individuals, protection against smallpox during the postexposure revaccination period may require T cell memory as an essential component for the rapid induction of protective cellular and humoral responses.     

Impact of measles in the United States

Measles has had a severe impact on children in the United States since colonial times. In the early decades of the 20th century, thousands of fatal measles infections were reported each year. During the 1950s an annual average of greater than 500,000 cases of measles and nearly 500 deaths due to measles were reported in the United States. Surveys indicated that 95% of the population had been infected with measles by the age of 15 years. The introduction of measles vaccine and its widespread use, which began in 1963, has had a major impact on the occurrence of measles in the United States. Reported numbers of cases, deaths due to measles, and complications of measles (e.g., encephalitis) have declined dramatically. Accompanying the decline in reported incidence of measles and following it by approximately seven years, has been a decline in the reported incidence of subacute sclerosing panencephalitis (SSPE). In recent years, the incidence of measles has dropped to levels that are less than 1% of those seen in the prevaccine era. In 1981, provisional figures indicated that only 10% of counties in the United States reported any cases of measles. The reported incidence in 1981 was 1.3 cases per 100,000 population, compared with an average incidence of 336.3 cases per 100,000 population in the decade 1950-1959. Thus, the impact of measles in the United States has been markedly reduced, and it is anticipated that indigenous transmission will be eliminated entirely from the country within the year.     

Humoral immune response of childhood acute lymphoblastic leukemia survivors against the measles,mumps, and rubella vaccination

ABSTRACT

Background: There is a great risk of infection with viral-vaccine-preventable diseases like measles, mumps, and rubella (MMR) infections after the end of chemotherapy treatment of children with acute lymphoblastic leukemia (ALL), which could have been prevented with MMR vaccination. Previous studies reported widely variable rates of seropositivity (seroprotection) for MMR after ALL treatment ends. Also, few studies evaluated the response to MMR booster vaccinations after the end of ALL treatment and reported unclear and difficult to interpret results.

Material and methods: This retrospective cross-sectional study evaluated the prevalence of seropositive (protection) antibody titer levels for MMR among ALL childhood survivors who were followed-up at Jeddah Oncology Center, Saudi Arabia. The aim of the study was also to investigate and analyze the response of seronegative patients to a booster MMR vaccination.

Results: Fifty-seven ALL children were evaluated. Thirty-five patients (61.4%) were seropositive/seroprotected and the remaining 22 patients (38.6%) were seronegative for MMR. ALL Children under the age of 5 years had a higher prevalence of seronegative titers. Interestingly, the prevalence of seroprotection decreased as the time interval increased post-treatment, while seroconversion rates after administering a booster MMR vaccine were 57.1%, 87.5%, and 78.6%, respectively for MMR.

Conclusion: We suggest the need for booster MMR vaccination, especially for ALL children under the age of 5 years and those who experienced a protracted time interval post-treatment.     

A 2-dose regimen of a recombinant hepatitis B vaccine with the immune stimulant AS04 compared with the standard 3-dose regimen of Engerix-B in healthy young adults

An open-label randomized study was undertaken to compare a 2-dose regimen (Months 0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months after the full vaccination course there was a 100% seroprotection rate (anti-HBs > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate with the licensed vaccine. The corresponding geometric mean titres were significantly higher for the novel vaccine compared to the standard vaccine: 15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml, respectively. There was a higher prevalence of local symptoms with the adjuvant vaccine (90% of doses) than with the standard vaccine (48% of doses). However, these symptoms (pain, swelling and redness) were predominantly of mild-to-moderate intensity and resolved rapidly without treatment. A 2-dose regimen of the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard regimen in healthy young adults. It is anticipated that the simplified vaccination schedule may improve compliance and reduce costs.     

Population immunity to measles in the United States, 1999

To estimate population immunity, we examined measles immunity among residents of the United States in 1999 from serological and vaccine coverage surveys. For persons aged >or=20 years, serological data from the third National Health and Nutrition Examination Survey (1988-1994) were used. For persons <20 years of age, immunity was estimated from results of the National Immunization Survey (1994-1998), state surveys of school entrants (1990-2000), and vaccine coverage surveys of adolescents (1997). To estimate immunity from vaccine coverage data, 95% vaccine efficacy was used for recipients of a single dose at >or=12 years of age and 99% vaccine efficacy was used for those with failure of a first dose who were revaccinated. Overall, calculated population immunity was found to be 93%. Although there was not much variation in immunity by region and state, in some large urban centers immunity among preschool-aged children was as low as 86%. Overall, geographic- and age-specific estimates of a high population immunity support the epidemiological evidence that measles disease is no longer endemic in the United States.     

Humoral immune responses in the hantavirus cardiopulmonary syndrome

The immunologic responses that mediate viral clearance of and recovery from hantavirus cardiopulmonary syndrome (HCPS) due to Sin Nombre (SN) virus are unknown. Serial serum samples from 26 patients with acute SN virus infection were tested for IgG, IgA, and IgM reactivity to recombinant viral nucleocapsid (N) and glycoprotein G1 antigens by a novel strip immunoblot assay. The titers of antibodies capable of neutralizing SN virus in vitro also were determined for each sample. At admission, patients with severe disease had lower titers of IgG antibodies to SN virus N antigen (P<.033) and lower neutralizing antibody titers (P<3.4x10-5), compared with patients with mild disease. These data suggest that a strong neutralizing antibody response may be a predictor of effective clearance of and recovery from SN virus infection and raise the possibility that passive immunotherapy may be useful in HCPS.     

Challenges to implementing second-dose varicella vaccination during an outbreak in the absence of a routine 2-dose vaccination requirement--Maine, 2006

In June 2005, the Advisory Committee on Immunization Practices (ACIP) recommended administering a second dose of varicella vaccine during outbreaks, supplementing the routine 1-dose requirement. From October 2005 to January 2006, a varicella outbreak occurred in Maine in a highly vaccinated elementary school population. We investigated the outbreak, held a school-based vaccination clinic, and assessed costs in implementing ACIP's outbreak-response recommendation. Parents completed questionnaires and case investigation interviews. Personnel at the Maine Center for Disease Control and Prevention, the school in which the outbreak occurred ("school A"), and physician offices completed economic surveys. Forty-eight cases occurred, with no hospitalizations or deaths. Vaccine effectiveness was 86.6% (95% confidence interval, 82.0%-90.1%). Of 240 eligible students, 132 (55.0%) received second-dose vaccination. Implementing ACIP's outbreak-response recommendation was challenging and cost approximately $26,875. Additionally, the routine 1-dose varicella vaccination policy did not confer adequate population immunity to prevent this outbreak. These findings support ACIP's June 2007 recommendation for a routine 2-dose varicella vaccination program.     

Humoral and cellular immune responses to Onchocerca volvulus infection in humans

Onchocerciasis is one of the major filarial diseases affecting humans and a leading cause of blindness. Control of the disease by chemotherapy and by elimination of the vector is not feasible in most areas of endemicity. The host immune response is thought to play a major role in the pathogenesis of complications. However, there is no clear evidence of protective immunity to reinfection in individuals who continue to be exposed to infective larvae. Antigens of Onchocerca volvulus are complex and show extensive cross-reactivity with other filarial parasites of humans and animals. Infection in humans results in the production of precipitating and reaginic antibodies to the parasite and in increases in levels of immunoglobulins that have no apparent specificity for parasitic antigens. Chronic antigenic stimulation in the presence of an antibody response leads to increased levels of circulating immune complexes. Cell-mediated immunity to parasite-derived antigens, as measured by migration inhibition, lymphocyte blastogenesis, and delayed skin-test reactivity, is decreased during infection. In addition, there is a decrease in delayed skin-test reactivity and in lymphocyte blastogenesis in response to unrelated antigens.     

Humoral and cellular immune responses to an envelope-associated antigen of herpes simplex virus.

The humoral and cellular immune responses of rabbits and guinea pigs to the envelope-associated antigen of herpes simplex virus type I were studied. Neutralizing antibody (at high titer) and lymphocytes reactive to herpes simplex virus were detected in both guinea pigs and rabbits after immunization with the antigen. In a standard assay of cellular immunity to herpes simplex virus, the antigen stimulated blast transformation of herpes simplex virus-reactive splenic lymphocytes in vitro. Furthermore, immunization of rabbits with the envelope-associated antigen protected the animals from a lethal dose of live herpes simplex virus. Thus an antigen of herpes simplex virus can be prepared which contains neither infectious nor noninfectious viral particles and which stimulates immunity to the virus in laboratory animals.     

Rifampin and cell-mediated immune responses in tuberculosis.

To estimate the potential adverse consequences of rifampin therapy on cell-mediated immunity in tuberculosis, we measured in vitro lymphocyte responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, and in vitro and in vivo responses to purified protein derivative tuberculin. Thirty-seven patients treated with therapeutic combinations containing rifampin were compared with 13 persons who had never received the drug. After initial improvement, responses to phytohemagglutinin became depressed in patients receiving rifampin for periods of 4 to 24 months. No significant changes were noted in lymphocyte responses to concanavalin A or pokeweed mitogen. In vitro and in vivo responses to purified protein derivative tuberculin were not altered. Because a favorable therapeutic outcome was achieved in all subjects, we concluded that rifampin does not have clinically significant immunosuppressive activity.     

Evolution of measles elimination strategies in the United States

There have been 3 efforts to eliminate measles from the United States since the introduction of measles vaccine in 1963. To date, 10 major lessons have been learned from elimination efforts. First, elimination requires very high vaccination-coverage levels by age 2 years. Second, school immunization requirements ensure high coverage rates among schoolchildren. Third, a second dose of measles vaccine is needed to achieve satisfactory levels of immunity. Fourth, school immunization requirements can also ensure delivery of a second dose. Fifth, coverage assessment is crucial. Sixth, measles surveillance is critical for developing, evaluating, and refining elimination strategies. Seventh, surveillance requires laboratory backup to confirm a diagnosis. Eighth, tracking measles virus genotypes is critical to determining if an endemic strain is circulating. Ninth, once endemic transmission has been interrupted, internationally imported measles cases will continue and will cause small outbreaks. Tenth, collaborative efforts with other countries are essential to reduce imported measles cases.     

Humoral and cellular responses to SARS-CoV-2 in patients with B-cell haematological malignancies improve with successive vaccination

Patients with haematological malignancies are more likely to have poor responses to vaccination. Here we provide detailed analysis of the humoral and cellular responses to COVID-19 vaccination in 69 patients with B-cell malignancies. Measurement of anti-spike IgG in serum demonstrated a low seroconversion rate with 27.1% and 46.8% of patients seroconverting after the first and second doses of vaccine, respectively. In vitro pseudoneutralisation assays demonstrated a poor neutralising response, with 12.5% and 29.5% of patients producing a measurable neutralising titre after the first and second doses, respectively. A third dose increased seropositivity to 54.3% and neutralisation to 51.5%, while a fourth dose further increased both seropositivity and neutralisation to 87.9%. Neutralisation titres post-fourth dose showed a positive correlation with the size of the B-cell population measured by flow cytometry, suggesting an improved response correlating with recovery of the B-cell compartment after B-cell depletion treatments. In contrast, interferon gamma ELISpot analysis showed a largely intact T-cell response, with the percentage of patients producing a measurable response boosted by the second dose to 75.5%. This response was maintained thereafter, with only a small increase following the third and fourth doses, irrespective of the serological response at these timepoints.