Immunogenicity and safety of aerosolized measles vaccine: Systematic review and meta-analysis

Low, Nicola; Kraemer, S.; Schneider, Martin; Restrepo, Ana Maria Henao

doi:10.1016/j.vaccine.2007.11.010

Cited by 74 publications

(51 citation statements)

References 27 publications

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“…This estimate was based on the 4 percentagepoint difference in a previous systematic review of studies involving children 10 to 35 months of age 13 ; in addition, with a bigger margin, aerosolized vaccine would not provide levels of protection required for herd immunity. 18 We assumed that exactly 90% of the children in each group would be seropositive at day 91, and we allowed for lower immunogenicity in children younger than 10 months of age.…”

Section: Discussionmentioning

confidence: 99%

“…Among children 10 to 35 months of age, the pooled seroconversion rate in five studies among those who received aerosolized vaccine against measles was 93.5% (95% confidence interval [CI], 89.4 to 97.7), and the pooled seroconversion rate in two studies among those who received the vaccine subcutaneously was 97.1% (95% CI, 92.4 to 100). 13 After subcutaneous vaccination, approximately 92% (interquartile range, 84 to 96) of children 9 to 10 months of age and 99% (interquartile range, 93 to 100) of children 11 to 12 months of age underwent seroconversion. 7 Given the established record of injectable measles vaccine, alternative delivery methods should show noninferiority.…”

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confidence: 99%

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A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles

et al. 2015

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BACKGROUNDAerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. METHODSWe conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. RESULTSA total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of −9.2 percentage points (95% CI, −12.2 to −6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of −9.3 percentage points [95% CI, −12.3 to −6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. CONCLUSIONSAerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity.

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confidence: 99%

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A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles

et al. 2015

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“…Aerosol vaccination offers many practical advantages over delivery via needles, and this study demonstrated that a single device can be used to vaccinate multiple subjects, which represents a highly cost-effective system for use in resource-poor settings. The feasibility of immunization by the inhalation of aerosolized vaccines for mass vaccination campaigns has been extensively evaluated for measles by the World Health Organization and was shown to be highly successful (36). The advantages associated with aerosol administration of TB vaccines are equally applicable to vaccines targeting not only other respiratory pathogens, such as influenza and pneumococcus, but also other pathogens, such as HIV, that enter via mucosal surfaces.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Safety and Immunogenicity of a Candidate Tuberculosis Vaccine, MVA85A, Delivered by Aerosol to the Lungs of Macaques

White¹,

Sibley²,

Dennis³

et al. 2013

Clin. Vaccine Immunol.

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b Tuberculosis (TB) is a reemerging disease. The only available vaccine, Mycobacterium bovis BCG, is delivered intradermally and confers highly variable efficacy against pulmonary disease. There is an urgent need for improved vaccination strategies. Murine studies suggest that immunizations delivered directly to the respiratory mucosa might be a more effective route of vaccination. This study compared the immunogenicity of a leading candidate tuberculosis (TB) vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in rhesus macaques, delivered either as an aerosol or as an intradermal boost immunization 12 weeks after an intradermal BCG prime vaccine. Aerosol vaccination was well tolerated. MVA85A delivered by aerosol or by intradermal injection induced antigen-specific immune responses in the periphery and the lung, with a trend toward the highest response when the compartment and route of delivery were matched. The ability of poxvirus-vectored vaccines delivered by the systemic route to induce responses in the mucosal immune compartment in macaques is in contrast to the independent compartmentalization of mucosal and systemic immune systems described in mice. Unlike intradermal vaccination, aerosol vaccination did not induce a detectable serum anti-vector antibody response. The delivery of vaccines to the lungs might provide an immunization strategy that limits the induction of systemic anti-vector immunity, which would be extremely useful in the development of improved vaccine strategies. This is the first study to show a recombinant MVA-vectored vaccine to be highly immunogenic when delivered by the aerosol route to nonhuman primates. These results provide important safety and proof-ofconcept data for further evaluation of this route of immunization for use in human clinical trials.

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“…Aerosol administration of aqueous vaccine is highly effective in boosting preexisting antibody and holds promise for use in older children (4)(5)(6)(7)(8)(9)(10)(11), but primary humoral and cellular immune responses vary with the age of vaccinees (12)(13)(14)(15).…”

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Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques

Lin

Griffin

Rota³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medical personnel and a cold chain, waste of vaccine in multidose vials and risks associated with needle use and disposal. Respiratory vaccine delivery could lower these barriers and facilitate sustained high coverage. We developed a novel single unit dose, dry powder live-attenuated measles vaccine (MVDP) for respiratory delivery without reconstitution. We tested the immunogenicity and protective efficacy in rhesus macaques of one dose of MVDP delivered either with a mask or directly intranasal with two dry powder inhalers, PuffHaler and BD Solovent. MVDP induced robust measles virus (MeV)-specific humoral and T-cell responses, without adverse effects, which completely protected the macaques from infection with wild-type MeV more than one year later. Respiratory delivery of MVDP was safe and effective and could aid in measles control.aerosol delivery | protective immunity | multifunctional T cells | antibody avidity M easles is a highly contagious viral disease. Before the availability of measles virus (MeV) vaccines, more than 130 million cases and 7-8 million deaths occurred annually. Intensive immunization efforts with the live attenuated measles vaccine (LAMV) given by injection have resulted in substantial decreases in global measles disease. However, with an estimated 164,000 deaths in 2008 (1), measles continues to be an important cause of child mortality, especially in less-developed regions of the world. The key to prevention of measles is achieving and sustaining high levels of population immunity through vaccination, and substantial challenges for high coverage remain in many countries. Some of the challenges to providing a first dose of measles vaccine to at least 95% of each birth cohort, plus a second dose to older children, are related to the method of vaccine delivery.Measles vaccine is given by injection, and this creates hurdles to sustained high coverage in many developing countries. First, there is often a shortage of the trained personnel needed for sterile reconstitution and safe injection of vaccine. Second, in most developing countries, lyophilized vaccine is in 5-10 dose vials that, after reconstitution, lose 30-50% potency in an hour at 37°C (2), so unused doses must be discarded. Third, contaminated needles and syringes create risks for transmitting bloodborne disease and require safe disposal.As a potential improvement, respiratory delivery of reconstituted liquid LAMV has been studied for more than three decades (3) but has never been licensed or widely used. Aerosol administration of aqueous vaccine is highly effective in boosting preexisting antibody and holds promise for use in older children (4-11), but primary humoral and cellular immune responses vary with the age of vaccinees (12-15).We have developed a dry powder formulation of ...

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Immunogenicity and safety of aerosolized measles vaccine: Systematic review and meta-analysis

Cited by 74 publications

References 27 publications

A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles

A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles

Evaluation of the Safety and Immunogenicity of a Candidate Tuberculosis Vaccine, MVA85A, Delivered by Aerosol to the Lungs of Macaques

Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques

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