Efficacy of Live Attenuated and Inactivated Influenza Vaccines in Schoolchildren and Their Unvaccinated Contacts in Novgorod, Russia

Rudenko, Larisa; Slepushkin, A. N.; Monto, Arnold S.; Kendal, Alan P.; Grigorieva, Elena; Burtseva, Elena; Rekstin, Andrey; Beljaev, A. L.; Bragina, V. E.; Cox, Nancy J.; Ghendon, Y. Z.; Alexandrova, Galina I.

doi:10.1093/infdis/168.4.881

Cited by 173 publications

(78 citation statements)

References 8 publications

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“…26,27 Pebody et al estimated that vaccinating 16 UK primary school children could prevent one primary care ILI consultation and vaccinating 317 children could prevent one influenza hospitalisation. 28 Similar herd protective effects from vaccinating school children have been demonstrated in Russia, 29 Japan, 30 and the US. 31,32 These beneficial effects for those outside the direct programme also contribute to national policy decisions on influenza vaccination.…”

Section: Introductionsupporting

confidence: 58%

Urgent challenges in implementing live attenuated influenza vaccine

Singanayagam

Zambon

Lalvani

et al. 2018

The Lancet Infectious Diseases

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SummaryConflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine (LAIV). LAIV appears to be protecting particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 (pH1N1) viruses. During the 2015/16 influenza season, when pH1N1 was the predominant virus, studies from the United States (US) reported a complete lack of effectiveness of LAIV in children. This led to a critical decision in the US to recommend that LAIV not be used in 2016/17 and to switch to the inactivated influenza vaccine. Other countries, including the UK, Canada and Finland, have continued to recommend use of LAIV. This policy divergence and uncertainty has far reaching implications for the entire global community, given the importance of LAIV production capability for pandemic preparedness. In this Personal View, we discuss possible explanations for the observed reduced effectiveness of LAIV and highlight underpinning scientific questions. Further research to understand the reasons for these observations is essential to enable informed public health policy and commercial decisions about vaccine production and development in coming years. 3 IntroductionInfluenza vaccination remains the main strategy to control the burden of seasonal influenza disease that affects 5-10% of adults and 20-30% of children, resulting in 250,000-500,000 deaths worldwide each year. 1,2 In the US, 140 million doses of vaccine are distributed each year and vaccination is estimated to prevent nearly a quarter of predicted influenza-associated deaths. 3 Vaccination is also the primary public health response to a global influenza pandemic.Influenza vaccines contain a mixture of three or four components designed to protect against the different viruses that circulate contemporaneously as seasonal influenza viruses. Currently, these are two influenza A viruses (H1N1 and H3N2 subtypes) and two influenza B viruses (Victoria and Yamagata lineages). Vaccine components are reviewed and updated regularly by the WHO in line with observed antigenic drift of influenza viruses.The traditional inactivated influenza vaccine (IIV) was introduced in the 1940s. IIV is administered by intramuscular/intradermal injection, is licensed for use in all ages and has a good safety record. However, effectiveness rates vary, averaging around 50-60%. 4,5 More recently, live attenuated influenza vaccine (LAIV) was demonstrated to have greater efficacy than IIV in children, with absolute efficacy rates of 75-80%. [6][7][8] Internal genes of LAIV viruses are derived from a cold-adapted, attenuated strain of virus, either Ann Arbor/1960 (from the US) or Leningrad/1957 (from Russia). Haemagglutinin (HA) and neuraminidase (NA) surface antigens are engineered to be representative of currently circulating strains. LAIV is nasally administered and vaccine viruses replicate only in the air-cooled environment of the human upper respiratory tract. This results in a mild and self-limiting infection; virus cannot replicate at t...

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Section: Introductionsupporting

confidence: 58%

Urgent challenges in implementing live attenuated influenza vaccine

Singanayagam

Zambon

Lalvani

et al. 2018

The Lancet Infectious Diseases

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“…However, little is known about the genetic make-up of B/USSR/60/69, which is in use as a MDV for influenza B vaccine viruses (Rudenko et al, 1993). This MDV has evolved from the propagation of the wt parental B/USSR/69 strain in chicken embryos for 17 passages at optimum temperature (32 uC) to yield B/ USSR/17/69 (Alexandrova, 1971), followed by an additional 60 passages at 25 u C (Alexandrova, 1996).…”

Section: Discussionmentioning

confidence: 99%

PB2 and PA genes control the expression of the temperature-sensitive phenotype of cold-adapted B/USSR/60/69 influenza master donor virus

Kiseleva

Voeten²,

Teley³

et al. 2009

Journal of General Virology

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The cold-adapted (ca) and temperature-sensitive (ts) influenza master donor virus (MDV) B/USSR/60/69 was derived from its wild-type parental virus after successive passages in eggs at 32 6C and 25 6C. This strain is currently in use for preparing reassortant influenza B vaccine viruses which are used in the Russian trivalent live attenuated influenza vaccine. Vaccine viruses are obtained by classical reassortment of MDV and a currently circulating wild-type virus. The phenotypic properties cold adaptation and temperature sensitivity are inherited from the six genes encoding the internal proteins of the MDV. However, the role of the individual gene segments in temperature sensitivity and thus attenuation is not known. In this study, 35 reassortant viruses of B/USSR/60/69 MDV with current wild-type non-ts influenza B viruses were generated in eggs or MDCK cells and studied in order to identify the genes responsible for their ts phenotype. For each virus the exact genome composition was determined as well as its ts phenotype. The results demonstrated that the polymerase PB2 and PA gene segments of B/USSR/60/69 MDV independently controlled expression of the ts phenotype of B/USSR/60/69 MDV-based reassortant viruses. The other genes coding for internal proteins played no role in this respect. This suggests that mutations in the polymerase genes PB2 and PA play an essential role in attenuation of B/USSR/60/69 MDV-based reassortant influenza B vaccine viruses.

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“…Data published from a study using the Russian intranasal vaccine showed better herd immunity for intranasal LAIV than inactivated vaccine. 127 Herd immunity is a crucial impact of mas vaccination programs; it is the immunity given to the whole population, even those who have not received a vaccine, because enough of the population (the herd) have received the vaccine that the infection cannot effectively spread. However, it should be noted that the Russian LAIV is administered in 2 doses 3 weeks apart, which increases cost and has the possibility of reducing compliance.…”

Section: Current Nasal Vaccine Productsmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

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Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...

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Efficacy of Live Attenuated and Inactivated Influenza Vaccines in Schoolchildren and Their Unvaccinated Contacts in Novgorod, Russia

Cited by 173 publications

References 8 publications

Urgent challenges in implementing live attenuated influenza vaccine

Urgent challenges in implementing live attenuated influenza vaccine

PB2 and PA genes control the expression of the temperature-sensitive phenotype of cold-adapted B/USSR/60/69 influenza master donor virus

Current prospects and future challenges for nasal vaccine delivery

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