**5. Future perspectives**

seroconversions were found among 44.8% of vaccinated persons [67]. These data indicate the substantial level of cross-reactive antibodies induced by LAIV against distant avian influenza viruses. The two doses of LAIV raised both CD4 and CD8 T-memory-cell responses in

**Vaccine Groups NI data Ref.**

**vaccination**

Placebo 0 (0) 9.9 7.5 0

LAIV 6 (33.3) 5.0 9.9 2.0\* [71]

**Geometric mean titers (GMT) GMT fold-rise Before** 

**After revaccination**

**Number of ≥2-fold antibody** 

**Table 3.** Serum NA-inhibiting antibodies against H5N2 LAIV 21 days after second vaccination.

**rises**

Previously, when studying the immunogenicity of inactivated vaccines based on potentially pandemic avian influenza viruses, both the experiment and the clinical trials showed a low immunogenicity of such preparations, according to generally accepted criteria for seroconversion of HI antibodies. The European Committee for the Control of Medicines has established the following criteria for the immunogenicity of vaccine preparations based on both epidemic and potentially pandemic influenza viruses: the multiplicity of antibody growths of at least 2.5 for individuals 18–60 years old and the development of reliable seroconversion in 40% of the vaccinated [68]. Obviously, the detection of only strain-specific HI antibodies is not sufficient to fully characterize the immunogenicity of the LAIV [69]. Moreover, it remains unclear what antibody titer can be considered protective against potentially pandemic viruses—1:20 or 1:40. Recently, it was shown that neuraminidase-inhibiting (NI) antibody titers better correlate with protection and can be an independent predictor of reduction of influenza disease severity [70]. Therefore, neuraminidase immunity should be considered when studying susceptibility after vaccination as a critical target in future influenza vaccine platforms. In this connection, the NI antibodies in the sera of volunteers after H5N2 immunization were estimated (**Table 3**). The two doses of the monovalent LAIV H5N2 raised a statistically significant increase in the NI antibodies against vaccine strain. More than twofold increase in antibodies was obtained among 19.5**–**33.3% of those vaccinated. The MN test and NI assay titers in the same sera of the vaccinated volunteers were 73.2% corresponded and suggested a statistically significant correlation between the values in antibody titers revealed

• The use of non-pathogenic avian viruses as a source of surface antigens combined with the use of cold-adapted "donors" of attenuation can be a significant advantage in the development of vaccine strains for LAIV against potentially pandemic influenza using classical genetic reassortment in CE. Low pathogenic avian influenza viruses do not contain a

peripheral blood of healthy volunteers on day 21 after boost immunization [67].

in both tests (p = 0.04).

**4. Conclusions**

LAIV H5N2 (6.9 log10 EID50/0.5 ml)

70 Influenza - Therapeutics and Challenges

\* P < 0.05.

> In the face of a pandemic threat, only live vaccines can eliminate the risk of losses from increased morbidity and mortality, as it was demonstrated in the cases with smallpox eradication and polio control. The conducted studies clearly showed that the classical genetic reassortment method allows obtaining high-yield, harmless and immunogenic LAIVs on the basis of an attenuated donor virus. In the post-pandemic period, when the direct threat of infection recedes, the main task is the search for optimal regimens for the use of new pandemic vaccines, including (1) the possibility of including such vaccine strains in the composition of polyvalent live vaccines; (2) prime-boost schemes using both LAIV and IIV; (3) the development of recommendations for vaccination of people with an increased risk of influenza infection complications; (4) a comprehensive study of the immune mechanisms of vaccination with influenza vaccines against emerging variant viruses; (5) the development of the most reliable and standardized assays to measure post-vaccination immune response.

> Currently, the FluMist LAIV, which was withdrawn from use in the USA and Europe in 2015 due to reduced LAIV effectiveness against A/H1N1pdm09, was returned to the practice by

the CDC's Advisory Committee on Immunization Practices (ACIP) (http://www.cidrap.umn. edu/news-perspective/2018/02/cdc-vaccine-panel-brings-back-flumist-2018-19-season). It was noted that after the replacement of A/H1N1pdm09 vaccine strain in the quadrivalent LAIV, an immune response was achieved similar to that of highly immunogenic seasonal A/H1N1 viruses circulating before 2009. Therefore, at present, much attention is paid to influenza vaccine strategies that target more broadly reactive antibodies which also apply to potentially pandemic vaccine strains.

**Author details**

Yulia Desheva1,2\*

**References**

\*Address all correspondence to: desheva@mail.ru

Experimental Medicine", Saint Petersburg, Russian Federation

Petersburg State University, Saint Petersburg, Russian Federation

2013;**17**:162-187. DOI: 10.1016/j.meegid.2013.02.020

World Health Organization. 1996;**74**(1):77-84. PMC: 2486837

Viruses. 2008;**2**(6):193-202. DOI: 10.1111/j.1750-2659.2008.00056.x

DOI: 10.1093/infdis/168.4.881

DOI: 10.1016/S0264-410X(00)00153-5

2004.01382.x

1 Virology Department, Federal State Budgetary Scientific Institution, "Institute of

2 Department of Fundamental Problems of Medicine and Medical Technologies, Saint

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