Assessment of immune responses to H5N1 inactivated influenza vaccine among individuals previously primed with H5N2 live attenuated influenza vaccine

Abstract

During the past decade, a number of H5 subtype influenza vaccines have been developed and tested in clinical trials, but most of them induced poor serum antibody responses prompting the evaluation of novel vaccination approaches. One of the most promising ones is a “prime-boost” strategy, which could result in the induction of prompt and robust immune responses to a booster influenza vaccine following priming with homologous or heterologous vaccine strains. In our study we evaluated immunogenicity of an adjuvanted A(H5N1) inactivated influenza vaccine (IIV) in healthy adult subjects who received A(H5N2) live attenuated influenza vaccine (LAIV) 1.5 years earlier and compared this with a group of naïve subjects. We found that priming with A(H5N2) LAIV induced a long-lasting B-cell immunological memory against influenza A(H5N1) virus, which was brought on by more prompt and vigorous antibody production to a single dose of A(H5N1) IIV in the primed group, compared to the naïve controls. Thus, by day 28 after the first booster dose, the hemagglutination inhibition and neutralizing (MN) antibody titer rises were 17.2 and 30.8 in the primed group, compared to 2.3 and 8.0 in the control group, respectively. The majority (79%) of the primed individuals achieved seroprotective MN antibody titers at 7 days after the first dose of the IIV. All LAIV-primed volunteers had MN titers ≥1:40 by Day 28 after one dose of IIV, whereas only 58% subjects from the naïve control group developed similar immune responses at this time point. The second A(H5N1) IIV dose did not increase the immune response in the LAIV-primed group, whereas 2 doses of IIV were required for naïve volunteers to develop significant immune responses. These findings were of special significance since Russian-based LAIV technology has been licensed to WHO, through whom the vaccine has been provided to vaccine manufacturers in India, China and Thailand — countries particularly vulnerable to a pandemic influenza. The results of our study will be useful to inform the development of vaccination strategies in these countries in the event of a pandemic

Safety, immunogenicity and infectivity of new live attenuated influenza vaccines

“…In contrast, in naïve individuals, two doses were required for a significant immune response to develop (TABLE 6). The antibodies induced by this prime-boost strategy were of high quality, as measured by their avidity and affinity [52][53][54]. Thus, such a vaccination regimen could have significant advantages in terms of availability and ease of administration of the priming vaccine and possibility of dose sparing for the booster vaccine.…”

“…These data prompted evaluation of the ability of pandemic LAIVs to prime for immunological memory, which can be unmasked by administration of a suboptimal dose of pandemic IIV several months or years later. To date, three studies have evaluated the priming effect of pandemic LAIVs: two with A/AA-backbone (H5N1 and H7N7) and one with Len/17 backbone (H5N2) [46,52,53]. All three studies revealed that priming with pandemic LAIV induced a long-lasting B-cell immunological memory in humans against antigenically related influenza virus, which was characterized by more prompt and vigorous antibody production to a single suboptimal dose of inactivated vaccine given 19-50 months later (TABLE 6).…”

Application of Method Based on in Vitro Antibody Quantification in PBMC Supernatant Samples for Immunogenicity Evaluation of a (H5n1) and a (H5n2) Potentially Pandemic Influenza Vaccines in Clinical Trials

“…Поэтому у участвовавших в нашем исследовании праймированных волонтеров ин-тенсивность накопления сывороточных антител к праймирующему вирусу А (H5N2) оказалась выше, чем к вакцинному вирусу А (H5N1), с ко-торым они встретились впервые. Необходимо от-метить значительный бустирующий эффект ИГВ H5N1 у праймированных ЖГВ H5N2 волонтеров, в отношении продукции сывороточных антител к вирусу H5N1, поскольку, как показано нами ра-нее, у непраймированных волонтеров синтез этих антител, в ответ на двойную инокуляцию ИГВ H5N1, оказался весьма низким [13]. Однако ко-личественные показатели (СГТ) секретируемых антител к обоим вирусам практически не отли-чались, поскольку, скорее всего, они проявляли специфичность только к общему гемагглютини-ну Н5, без «наслоения» кросс-реактивных анти-тел к консервативным белковым структурам вируса, выявляемым при исследовании в ИФА сывороточных антител.…”

Live Attenuated Reassortant Vaccines Based on A/Leningrad/134/17/57 Master Donor Virus Against H5 Avian Influenza

“…The idea to administer of a combination of two different types of influenza vaccines led to the development of novel vaccination approach – so called prime–boost strategy, which could result in induction of significant immune response to a booster IIV following priming with homologous or heterologous LAIV [53-55]. Similar to these prime–boost studies, assessment of immune responses to tT (H5N1) inactivated influenza vaccine among individuals previously primed with Len–tT (H5N2) LAIV was performed [56]. Data revealed that priming with Len–tT LAIV induced a long–lasting B–cell immunological memory in subjects against antigenically related influenza virus, which was characterized by more prompt and vigorous antibody production to a single dose of H5–IIV given 18 months later.…”