A Clinical Study to Assess the Safety and Immunogenicity of Attenuated Measles Vaccine Administered Intranasally to Healthy Adults

Simon, Jakub K.; Pasetti, Marcela F.; Viret, Jean-François; Mischler, Robert; Muñoz, Alma; Lagos, Rosanna; Levine, Myron M.; Campbell, James D.

doi:10.4161/hv.3.2.3877

Cited by 12 publications

(15 citation statements)

References 16 publications

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“…These observations emphasize the critical roles for successful respiratory measles immunization of small particle size and the device used for delivery. Previous studies using liquid LAMV delivered intranasally with a sprayer designed for deposition in the nose only (large droplets) did not demonstrate robust immune responses (31), whereas the powder used in this study was suitable for deep lung delivery. These results suggest that delivery of a small particle-size powder vaccine via the nasal route may be an option for measles vaccination.…”

Section: Discussionmentioning

confidence: 78%

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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Section: Discussionmentioning

confidence: 78%

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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“…with the live attenuated Moraten measles vaccine could elicit a protective immune response comparable to that induced by routine subcutaneous (s.c.) vaccination (16). We found that subjects who received the vaccine s.c. responded with a significant increase in serum plaque reduction virus-neutralizing (PRN) antibodies, the measles correlate of protection (5).…”

mentioning

confidence: 81%

“…Intranasal administration was performed by inserting the tip of an Accuspray device (Becton Dickinson) inside the nose of an upright individual, holding the device at approximately 45°to the ground, and depressing the plunger to spray toward the occiput. The clinical assessment following vaccination is described in detail elsewhere (16).…”

Section: Methodsmentioning

confidence: 99%

“…A clinical study was performed with healthy adult volunteers aged 18 to 45 years who were recruited and enrolled in Santiago, Chile, between September and October 2004 as described elsewhere (16). Serum PRN antibodies against MV were measured in all volunteers before vaccination, and those with titers of Ն200 mIU/ml were considered immune to measles (5).…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, subjects who received the vaccine i.n. failed to develop systemic PRN responses (16). In this study, we examined the mucosal immune responses in these subjects in relation to their preexisting serum PRN antibody status and demonstrated that nonimmune individuals immunized i.n.…”

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confidence: 99%

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Mucosal IgA Responses in Healthy Adult Volunteers following Intranasal Spray Delivery of a Live Attenuated Measles Vaccine

Simon

Ramírez

Cuberos

et al. 2011

Clin Vaccine Immunol

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Measles remains an important cause of morbidity and mortality among children in the developing world. The goal of this study was to examine measles virus-specific mucosal immune responses in healthy immune (n ‫؍‬ 24; plaque reduction neutralization [PRN] titers of >200 mIU/ml) and nonimmune (n ‫؍‬ 24) young adult volunteers who received the monovalent Moraten measles vaccine via intranasal (spray delivery) or subcutaneous immunization. Serum, oral fluid, and nasal wash samples were examined for measles virus-specific and total IgG and IgA on day 0 (prior to vaccination) and on days 14, 28, and 90 after vaccination. Nonimmune subjects vaccinated subcutaneously developed high levels of measles virus PRN, IgG, and IgA antibodies in serum, oral fluid, and nasal washes. Total IgG and secretory IgA (sIgA) titers were increased in nasal washes, and total IgG was increased in oral fluid specimens. There was a strong correlation between PRN and measles virus-specific IgG titers measured in serum, oral fluid, and nasal washes, whereas a weak correlation was found between PRN and measles virus-specific IgA titers. Notably, intranasal measles vaccination resulted in increased production of measles virus-specific sIgA in oral fluid and nasal washes in nonimmune individuals, without evidence of a systemic immune response. In contrast, no significant vaccine-induced responses were observed in immune subjects, regardless of the route of immunization. These results demonstrate that (i) intranasal measles immunization can elicit a mucosal response independent of the induction of serum antibodies and (ii) both mucosal and systemic antibody responses following nasal or subcutaneous immunization are blunted by preexisting measles immunity.

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Alternative vaccine delivery methods

Weniger¹,

Papania²

2013

Vaccines

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A Clinical Study to Assess the Safety and Immunogenicity of Attenuated Measles Vaccine Administered Intranasally to Healthy Adults

Cited by 12 publications

References 16 publications

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

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

Mucosal IgA Responses in Healthy Adult Volunteers following Intranasal Spray Delivery of a Live Attenuated Measles Vaccine

Alternative vaccine delivery methods

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