Aerosolized MMR vaccine: evaluating potential transmission of components to vaccine administrators and contacts of vaccinees.

Although numerous operative and immunological advantages accompany aerosol immunization, potential vaccine virus transmission from the aerosol device to vaccine administrators or from aerosol vaccinees to their contacts requires further study. We conducted a clinical and serological follow-up study of vaccine administrators and matched classroom or household contacts of young adults who received the MMR vaccines by aerosol or injection. Differences in incidence of clinical adverse events between vaccinees and contacts were not statistically significant. No seroresponses to any components of MMR vaccine were noted among 25 matched contacts of persons receiving injected vaccines, and only one equivocal seroresponse was noted among 25 matched contacts of aerosol recipients. No seroresponses were observed in 3 persons who administered aerosol vaccine. The composite findings of this study provide additional evidence of the safety of this approach.

Booster immune response in children 6-7 years of age, randomly assigned to four groups with two MMR vaccines applied by aerosol or by injection.

IMPORTANCE: Aerosol immunization may be a useful tool to reach and sustain the elimination of measles, rubella, and congenital rubella syndrome. We compared booster seroresponses to aerosolized or injected MMR vaccines containing different strains of measles (Attenuvax or Edmonston-Zagreb) and mumps (Jeryl-Lynn or Leningrad-Zagreb). OBJECTIVE: To assess the safety and immunogenicity of two MMR: Vaccines administered by aerosol. METHODS: A randomized and controlled clinical trial was conducted to evaluate the safety and booster responses to the MMR SII (Serum Institute of India) and MMR II (Merck Sharp & Dhome) vaccines, both of which were administered by aerosol (ae) or injection (inj) to Mexican children aged 6-7 years in elementary schools. The seroresponses were evaluated by PRN (measles) and ELISA (rubella and mumps). Adverse events were followed-up for 28 days after the immunization. RESULTS: Two hundred and fifty-three of 260 children completed the one-month follow-up. All participants reached protective seropositivity for measles and rubella after immunization, and 98.3 to 100% reached protective seropositivity for mumps (p=0.552). The proportions of the seroresponses (a 2-fold rise from the baseline antibody titers) to measles were 38.3% for MMR SII (ae), 31.3% for MMR II (ae), 37.5% for MMR SII (inj), and 44.6% for MMR II (inj) (p=0.483). The seroresponses for rubella were 26.7% for MMR SII (ae), 31.3% for MMR II (ae), 46.9% for MMR SII (inj), and 40.0% for MMR II (inj) (p=0.086). The seroresponse to mumps were 31.7% for MMR SII (ae), 25.0% for MMR II (ae), 48.4% for MMR SII (inj), and 53.9% for MMR II (inj) (p=0.002). The difference in the seroresponse of a 4-fold rise from the baseline antibody titers was not statistically significant. Only mild adverse events were noted. CONCLUSION: Aerosolized vaccines were as safe and as immunogenic as injected vaccines. PROTOCOL REGISTRATION: CMN 2010-005 (National Regulatory Authority).

Successful seroresponses to measles and rubella following aerosolized Triviraten vaccine, but poor response to aerosolized mumps (Rubini) component: comparisons with injected MMR.

Seroresponses to measles, rubella and mumps were evaluated following the injection of MMR II and injection or aerosol administration of Triviraten in young adults. Response to aerosolized Rubini mumps strain was a focus of interest, given robust responses to aerosolized mumps vaccine (Leningrad-Zagreb strain) in a prior study using aerosolized MMR vaccine. The aerosolized Edmonston-Zagreb (EZ) measles vaccine was significantly more immunogenic than injected EZ vaccine, and comparable to results following injected Moraten measles vaccine having twice the dosage. Responses to rubella were comparable in the three MMR study groups. Aerosolized Rubini vaccine was very highly and unexpectedly less immunogenic than either injected Rubini or Jeryl-Lyn strains. The high attenuation of Rubini vaccine appears to have limited its affinity for respiratory tract receptors, which may underlie its lack of clinical effectiveness.

Antibody persistence in young adults 1 year after MMR immunization by aerosol or by subcutaneous route.

Information on antibody persistence after aerosol revaccination with MMR components is limited. Thus, antibody titers were determined in 283 adult participants in a MMR vaccine trial 12 months after revaccination. One group had received aerosolized Triviraten vaccine while two other groups received either injected Triviraten or MMR II vaccine. Both MMR vaccines contained the same rubella strain, but different measles and mumps strains. Seropositivity to measles persisted in 98% of aerosolized vaccine recipients, 92% of injected Triviraten, and 95% of injected MMR II. All participants in the three groups retained seropositivity to rubella, while less than 50% remained seropositive to mumps.

A new, rapid, and promising approach to aerosol immunization: inflatable bags and valved masks.

Booster doses of MMR vaccine equal in dosage to injected doses were aerosolized into a 3/4 l bag that inflated in 4s. The bag was then attached to valved masks, and its contents rapidly inhaled in one or two deep breaths by preschool Mexican children. Antibody responses in the children exposed to the aerosolized measles component were superior to those noted after injection, while responses to the mumps and rubella components were equivalent. The new method appears to be effective, safe, and has several advantages over previously used methods. Further explorations of the approach seem merited.

Aerosol and subcutaneous measles vaccine: measles antibody responses 6 years after re-vaccination.

There are no large-scale data on the long-term persistence of measles antibody after vaccination by the aerosol route. We therefore followed-up South African schoolchildren 6 years after their re-vaccination with Edmonston-Zagreb (EZ) and Schwarz (SW) measles vaccine given by aerosol and subcutaneous routes. Measles antibody levels and the proportion of children who were seropositive at year 6 remained significantly higher in the Edmonston-Zagreb aerosol group compared to the groups that received Schwarz or Edmonston-Zagreb vaccine subcutaneously. Measles re-vaccination by aerosol evokes a stronger and much longer lasting antibody response than injected vaccine and should thus provide more durable protection against measles.

Aerosol measles vaccination in macaques: preclinical studies of immune responses and safety.

The comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different routes of administration in the immunocompetent and the immunocompromised host. Immunogenicity and protective efficacy of aerosol vaccination using devices similar to those previously used in humans were comparable to those in animals vaccinated by injection. No evidence for a safety hazard associated with the route of vaccination was detected. The results of this study support further clinical evaluation of aerosol vaccination for measles.

Evaluation of immunogenicity and side effects of triple viral vaccine (MMR) in adults, given by two routes: subcutaneous and respiratory (aerosol).

Adult volunteers from two neighboring health centers were immunized with measles, mumps, rubella vaccine (MMR, Serum Institute of India Ltd.), either given by traditional injections or by an aerosol delivered to the respiratory tract. Baseline and one month post vaccination samples were taken and simultaneously assayed for all three antigens. Subjects were followed-up for temporally associated events after vaccination. The aerosol route was superior for measles, mumps and rubella when baseline titers were controlled for in multivariate analysis. Frequencies of post-vaccination events did not differ with statistical significance between the groups. Further evaluation of the aerosol route for MMR immunization appears warranted.

Risk of Haemophilus influenzae type b meningitis in Polish children varies directly with number of siblings: possible implications for vaccination strategies.

BACKGROUND: In the absence of an effective vaccine, Haemophilus influenzae type b (Hib) meningitis has frequently been found to be the most common bacterial meningitis among children less than or equal to 5 years of age. This study was conducted prior to the introduction of Hib vaccine in Poland, and is the first case-control study of Hib meningitis in this country. METHODS: A 1:3 matched case-control study was nested within a population-based surveillance study of Hib meningitis in children less than or equal to 5 years old in Poland. Controls were matched on the case's age at onset of disease and immunization center. RESULTS: Having one or more siblings is a highly significant risk factor for Hib meningitis and, under the rare disease assumption, risk increases linearly with the increase in the number of siblings. The size of the living area of the home was not itself a significant risk factor for disease. Breast-feeding was not protective in contrast to previous studies. Childcare outside of the home was a significant risk factor for Hib meningitis especially among children greater than 16 months of age, whereas the effect of sibling number on Hib meningitis was much greater among the younger children. CONCLUSION: Risk of Hib meningitis approximately doubles for every unit increase in the number of siblings. Routine vaccination of Polish infants who have two or more siblings could potentially prevent half of the Hib meningitis cases.

Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren.

OBJECTIVE: To compare antibody responses and side-effects of aerosolized and injected measles vaccines after revaccination of children enrolling in elementary schools. METHODS: Vaccines for measles (Edmonston-Zagreb) or measles-rubella (Edmonston-Zagreb with RA27/3) were given by aerosol or injection to four groups of children. An additional group received Schwarz measles vaccine by injection. These five groups received vaccines in usual standard titre doses. A sixth group received only 1000 plaque-forming units of Edmonston-Zagreb vaccine by aerosol. The groups were randomized by school. Concentrations of neutralizing antibodies were determined in blood specimens taken at baseline and four months after vaccination from randomized subgroups (n = 28-31) of children in each group. FINDINGS: After baseline antibody titres were controlled for, the frequencies of fourfold or greater increases in neutralizing antibodies did not differ significantly between the three groups that received vaccine by aerosol (range 52%-64%), but they were significantly higher than those for the three groups that received injected vaccine (range 4%-23%). Mean increases in titres and post-vaccination geometric mean titres paralleled these findings. Fewer side-effects were noted after aerosol than injection administration of vaccine. CONCLUSION: Immunogenicity of measles vaccine when administered by aerosol is superior to that when the vaccine is given by injection. This advantage persists with aerosolized doses less than or equal to one-fifth of usual injected doses. The efficacy and cost-effectiveness of measles vaccination by aerosol should be further evaluated in mass campaigns.