Localized Mucosal Response to Intranasal Live Attenuated Influenza Vaccine in Adults

Abstract

Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

“…These differences may be due in part to preexisting immunity present in most adults due to multiple prior exposures to live circulating influenza virus strains and to previous influenza vaccinations. In a recent report, Barría et al (15) evaluated HAI responses to H1N1 HA with respect to preexisting antibody titers and noted that the small subset of adults achieving a 4-fold or higher HAI response to H1N1 HA following LAIV vaccination had low to negative prevaccination HAI titers. The relative immunological naiveté of young children allows more prolonged replication of LAIV in the upper respiratory tract, which may result in greater stimulation of multiple T and B cell subsets.…”

“…Host status can have major effects on vaccineinduced responses. For example, preexisting immunity can inhibit the response to a vaccine that must infect and replicate for optimal immunogenicity (15,16). Furthermore, relative immunodeficiencies can limit optimal vaccine-induced responses and may have a greater effect in reducing responses to IIV with fewer natural adjuvant properties.…”

Noninvasive vaccination as a casus belli to redeem vaccine value in the face of anti-vaccine movements

“…Since the mucocutaneous barrier is in constant contact with a myriad of commensal microbes and innocuous antigens, the periphery immune system is required to perform an arduous duty by playing dual roles on diametrically opposed mechanisms between protective immunity and immune tolerance. Emerging evidence has shown that the periphery immune system is indeed more competent than its deep-tissue counterpart in restraining inflammation in order not to mistakenly summon a detrimental immune overdrive during daily encounter with environmental microbes [18,34,35].…”

“…In contrast to i.m. vaccination, nasal spray of LAIV induces neither systemic inflammation [34,46] nor vaccineassociated enhanced respiratory disease [47]. Since LAIV-induced seroconversion rate is inversely correlated with pre-existing levels of granulocyte colony-stimulating factor (G-CSF) which is associated with recruitment of neutrophils [34], it is hypothesized that phagocytosis along the mucosal barrier may restrict LAIV dissemination, allowing nasal vaccines to focus on antigen presentation at mucosal sites with diminished potential to induce systemic inflammation by preventing LAIV from entering circulation.…”

“…vaccination, nasal spray of LAIV induces neither systemic inflammation [34,46] nor vaccineassociated enhanced respiratory disease [47]. Since LAIV-induced seroconversion rate is inversely correlated with pre-existing levels of granulocyte colony-stimulating factor (G-CSF) which is associated with recruitment of neutrophils [34], it is hypothesized that phagocytosis along the mucosal barrier may restrict LAIV dissemination, allowing nasal vaccines to focus on antigen presentation at mucosal sites with diminished potential to induce systemic inflammation by preventing LAIV from entering circulation. Mechanistically, antigen presentation and immune memory do not require absorption of nasal vaccines into circulation because pulmonary defenses may be bolstered by transient assembly of tertiary lymphoid structures post-vaccination in the lungs [48,49], and memory T cells in mice and humans could be generated and maintained in compartmentalized niches within lungs [50], independent of secondary lymphoid organs.…”