Understanding Immunity in Children Vaccinated With Live Attenuated Influenza Vaccine

Shannon, Ian; White, C. L.; Nayak, Jennifer L.

doi:10.1093/jpids/piz083

Cited by 14 publications

(12 citation statements)

References 51 publications

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“…There are two major types of licensed IAV vaccines for clinical application: inactivated influenza vaccines (IIV) and live-attenuated influenza vaccines (LAIV). IIV mainly induce humoral but not cell-mediated immune responses (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Therefore, IIV offers limited protection if the seasonal vaccines do not antigenically match the predicted circulating IAV strains (9,10,13,15).…”

Section: Introductionmentioning

confidence: 99%

“…heterologous IAV strains, which is important in the case of antigenic mismatch between vaccine and circulating strains (9,10,(27)(28)(29)(30)(31)(32)(33)(34)(40)(41)(42)(43). Unfortunately, because safety concerns, the United States (U.S.) licensed LAIV remains restricted to 2-to 49-year old healthy, non-pregnant persons.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, since LAIV are delivered nasally, they induce strong mucosal immunity at the site of infection (8, 35, 39). Finally, due to their induction of a cross-reactive cell-mediated immunity, which targets conserved viral proteins, LAIV confer more efficient protection against heterologous IAV strains, which is important in the case of antigenic mismatch between vaccine and circulating strains (9, 10, 27-34, 40-43). Unfortunately, because safety concerns, the United States (U.S.) licensed LAIV remains restricted to 2- to 49-year old healthy, non-pregnant persons.…”

Section: Introductionmentioning

confidence: 99%

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A single amino acid substitution in PB1 of pandemic H1N1 with A/Ann Arbor/6/60 master donor virus mutations as a novel live-attenuated influenza virus vaccine

Nogales

Steel

Liu

et al. 2022

Preprint

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Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year old healthy and non-pregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The United States (U.S.) licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A single amino acid substitution in PB1 of pandemic H1N1 with A/Ann Arbor/6/60 master donor virus mutations as a novel live-attenuated influenza virus vaccine

Nogales

Steel

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In the United States, seasonal vaccines are available in the form of either recombinant proteins, inactivated influenza (IIV) vaccines, and/or live attenuated influenza virus (LAIV) vaccines. It is known that LAIVs can mimic a natural influenza infection, which can stimulate both mucosal and cellular immunity [ 15 , 16 , 17 ]. However, less than optimal vaccine efficacy of the FluMist LAIV in the 2013–2014 and 2015–2016 seasons, particularly in young children, prompted the CDC to temporarily recommend against its use in 2016 [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

Cardenas-Garcia

Santos

et al. 2021

Vaccines

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Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children, and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of an HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation to stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations, along with attenuating mutations E580G and S660A, in PB1 of B/Bris (B/Bris PB1att 4M). Serial passages of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

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“…In the United States, seasonal vaccines are available in the form of either recombinant proteins, inactivated influenza (IIV) vaccines and/or live attenuated influenza virus (LAIV) vaccines. It is known that LAIVs can mimic a natural influenza infection, which can stimulate both mucosal and cellular immunity [15][16][17]. However, less than optimal vaccine effectiveness of the FluMist LAIV in the 2013-2014 and 2015-2016 seasons, particularly in young children, prompted CDC to temporarily recommend against its use in 2016 [18].…”

Section: Introductionmentioning

confidence: 99%

Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

Mo¹,

Cardenas-Garcia²,

Santos³

et al. 2021

Preprint

View full text Add to dashboard Cite

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of a HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation for stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations along with attenuating mutations E580G and S660A in PB1 of B/Bris (B/Bris PB1att 4M). Serial passage of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

show abstract

Understanding Immunity in Children Vaccinated With Live Attenuated Influenza Vaccine

Cited by 14 publications

References 51 publications

A single amino acid substitution in PB1 of pandemic H1N1 with A/Ann Arbor/6/60 master donor virus mutations as a novel live-attenuated influenza virus vaccine

A single amino acid substitution in PB1 of pandemic H1N1 with A/Ann Arbor/6/60 master donor virus mutations as a novel live-attenuated influenza virus vaccine

Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

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