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

Abstract

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.

Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein

“…Remarkably, both recombinant MV-SARS vectors also induced SARS-CoV specific IgA, whereas the subunit reference vaccine did not. This raises an interesting point since several clinical studies already evidenced that parenteral administration of live attenuated measles vaccine to children stimulates secretory IgA responses in nasal washes (Bellanti et al, 2004;Simon et al, 2011). Although we did not assess the ability of recombinant MV-SARS to induce secretory IgA in the lungs and upper respiratory tract of immunized mice, this result is strongly indicative of the potential of MV-SARS to induce SARS-CoV specific secretory IgA responses.…”

The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches

“…For example, the median neutralizing antibody titer for our cohort was 844 mIU/ml (interquartile range: 418–1752; minimal value: 45; maximal value: 7723) 7.4 years after two doses of MMR vaccine, and the median IFN-γ ELISPOT response was 36 (interquartile range: 13–69; minimal value: −17; maximal value: 208) IFN-γ-positive spot-forming units (SFUs) per 200,000 cells, suggesting substantial biological variability, waning immunity and potential susceptibility to measles [17,22]. Our research team [23] and others [24–26,203] have called for maintenance of and/or progress toward measles elimination, recognizing the related challenges, including the need for research on determinants of measles vaccine response, and the development of improved measles vaccines.…”

Current prospects and future challenges for nasal vaccine delivery

“…57 Many published studies have shown that nasally administered vaccines induce serum IgG and mucosal IgA that are important for deliberating enhanced efficacy of vaccine. 57,58 The enhanced induction of mucosal IgA antibodies has been shown to play a significant role in neutralizing pathogens such as Streptococcus pneumonia 59 and measles viruses 60 and preventing further infection. Moreover, intranasal immunization has also been reported to induce cross-reactive antibodies that might be indicative of cross-protection.…”