Influenza Vaccine: An Engineering Vision from Virological Importance to Production

S. Furkan Demirden,Kadir Alptekin,Ilgin Kimiz-Gebologlu,Suphi S. Oncel 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.5

According to data from the World Health Organization (WHO) every year, millions of people are affected by flu. Flu is a disease caused by influenza viruses. For preventing this, seasonal influenza vaccinations are widely considered the most efficient way to protect against the negative effects of the flu. To date, there is no “onesize- fits-all” vaccine that can be effective all over the world to protect against all seasonal or pandemic influenza virus types. Because influenza virus transforms its genetic structure and it can emerges as immunogenically new (antigenic drift) which causes epidemics or new virus subtype (antigenic shift) which causes pandemics. As a result, annual revaccination or new subtype viral vaccine development is required. Currently, three types of vaccines (inactivated, live attenuated, and recombinant) are approved in different countries. These can be named “conventional influenza vaccines” and their production are based on eggs or cell culture. Although, there is good effort to develop new influenza vaccines for broader and longer period of time protection. In this sense these candidate vaccines are called “universal influenza vaccines”. In this article, after we mentioned the short history of flu then virus morphology and infection, we explained the diseases caused by the influenza virus in humans. Afterward, we explained in detail the production methods of available influenza vaccines, types of bioreactors used in cell culture based production, conventional and new vaccine types, and development strategies for better vaccines.

분편 인플루엔자백신(split influenza vaccine)의 임상효과 및 면역원성에 관한 연구

우흥정,김동림,정희진,천병철,이주연,안정배,김지희,박찬,신영규,김우주,김민자,박승철 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.1

목적 : 아단위 인플루엔자 백신 접종 후 백신의 인플루엔자 예방효과, 인플루엔자 방어 항체형성, 인플루엔자 백신의 안전성을 조사하고자 하였다. 방법 : 총 571명을 대상으로 인플루엔자 백신 접종을 하였고, 이들 접종자에서 인플루엔자 양질환의 이환을 조사하여 인플루엔자 백신의 인플루엔자예방효과를 알아보았고, 백신의 접종 전 및 접종 4주 후 혈청에서 혈구응집억제물(Hemagglutination Inhibition : HAI) 항체 검사를 실시하여 백신의 방어항체생성을 조사하였고, 백신의 안전성을 알아보기 위해 백신접종 후 1주일 이내의 부작용을 조사하였다. 결과 :백신 접종군과 백신 비접종군에서 인플루엔자 양 질환의 이환을 조사한 결과 접종군 28.35%, 비접종군 35.88%으로 나왔으며, p 값이 0.001로 통계적으로 접종군에서 유의하게 낮았고, 인플루엔자 양 질환의 예방 효과는 20.97%를 보였다. 백신의 방어항체 형성의 평가를 위해 유럽의 인플루엔자 백신 허가 기준을 조사하였는데 B/Guangdong/5/94균주의 백신접종 후 항체가 40이상의 비율을 제외한 다른 기준은 모두 만족 시켰다. 부작용은 전체 조사자 521명중 149명(29%)으로 주로 접종 부위의 국소 부작용을 호소했고, 전신 부작용은 2% 내외였으며 특별히 심각한 부작용은 발견되지 않았다. 결론 : 분편 인플루엔자 백신은 인플루엔자양질환의 예방과 방어항체생성에 효과 있으며 안전한 것으로 사료된다. Background : The safety and effectiveness of influenza vaccine are well known in developed country. The influenza vaccination has been recommended as one of the tentative immunization schedule for indicated persons since 1997 in Korea. But there are still no available data about them, even though nearly 5 million doses of influenza vaccine were used in 1997-1998 season. So it is immediately needed to investigate the safety. efficacy and immunogenicity of influenza vaccine among Korean. Methods : We studied the clinical efficacy of influenza vaccine by monitoring Occurrence of influenza-like illness in influenza risk group(vaccination ; 300, non-vaccination; 215) from December in 1997 to March in 1998. We used the split quadrivalent influenza vaccine containing 15 microgram of hemagglutinin of A/Beijing/262/95(HlNl), A/Wuhan/359/95(H3N2), B/Mie/1/93 and B/Guangdong/5/94. Hemagglutination inhibition(HA1) antibody titers were determined before immunization and 1 months after vaccination And we evaluated adverse effect of influenza vaccination at 7 days after vaccination. Results : Influenza vaccination was associated with si@icant reductions in influenza-like spptoms(vaccination group; 28.35%, non-vaccination group, 35.88%, p=0.001). The preventive effect of influenza-like i3lne.s among influenza risk goup was 20.97%. And immunogenicity of influenza A and B exceeded all of the European licensure criteria for immunogenicity except postvaccination proportion of titers 240 of B/Guangdong/5/94 strain. And the adverse effects were mainly local injection site problem and no serious adverse effect was noted. Conclusion : Split influenza vaccine is safe, inmunogenic and eff'tive in influenza risk group in Korea.

Perception and Attitudes of Korean Obstetricians about Maternal Influenza Vaccination

노지윤,서유빈,송준영,최원석,이재갑,정은주,강성휘,최민주,전지호,윤진구,이샘나,현학준,이진수,정호진,정희진,김우주 대한의학회 2016 Journal of Korean medical science Vol.31 No.7

Pregnant women are prioritized to receive influenza vaccination. However, the maternal influenza vaccination rate has been low in Korea. To identify potential barriers for the vaccination of pregnant women against influenza, a survey using a questionnaire on the perceptions and attitudes about maternal influenza vaccination was applied to Korean obstetricians between May and August of 2014. A total of 473 respondents participated in the survey. Most respondents (94.8%, 442/466) recognized that influenza vaccination was required for pregnant women. In addition, 92.8% (410/442) respondents knew that the incidence of adverse events following influenza vaccination is not different between pregnant and non-pregnant women. However, 26.5% (124/468) obstetricians strongly recommended influenza vaccination to pregnant women. The concern about adverse events following influenza vaccination was considered as a major barrier for the promotion of maternal influenza vaccination by healthcare providers. Providing professional information and education about maternal influenza vaccination will enhance the perception of obstetricians about influenza vaccination to pregnant women and will be helpful to improve maternal influenza vaccination coverage in Korea.

6-59개월 미만 자녀를 가진 보호자에게 홍보물 교육 유무에 따른 인플루엔자 및 인플루엔자 백신접종에 관련한 인식도 조사

김윤모,임중섭,김윤경,은병욱,조대선,김동호,Kim, Yoon Mo,Lim, Jung Sub,Kim, Yun Kyung,Eun, Byung Wook,Jo, Dae Sun,Kim, Dong Ho 대한소아감염학회 2020 Pediatric Infection and Vaccine Vol.27 No.1

Purpose: To compare differences and changes in the parents' awareness regarding influenza and influenza vaccination for their children according to educational intervention. Methods: This study involved 1,034 parents with children aged 6-59 months, who lived in five areas in northern Seoul and Gyeonggi Province in 2015; the study was conducted using the questionnaire survey method. Survey items included awareness regarding influenza and influenza vaccination for children and future intentions of influenza vaccination and the underlying reasons. The participants were divided into 3 groups and differences according to education (group A: no education, group B: provided education) and the changes before and after education (group C) were analyzed. Results: Differences according to education between groups A and B were seen in the recognition of high-risk of influenza in their children, effectiveness of influenza vaccination, and cost of the influenza vaccine. Changes before and after education in group C were seen in the recognition of high-risk of influenza in their children, safety of influenza vaccination, cost of the influenza vaccine, and negativity toward the influenza vaccine. Conclusions: Educated parents were more aware regarding influenza and influenza vaccination for their children aged 6-59 months.

임신부의 인플루엔자 백신 접종률 및 관련요인

김미정,이광수,김아름,정문현,박신구,이병익,이진수,이승연,손동욱,박지현 대한감염학회 2009 Infection and Chemotherapy Vol.41 No.6

Background:During seasonal influenza epidemics and previous pandemics, pregnant women have been at increased risk for complications related to influenza infection. Although influenza vaccination has been widely recommended to pregnant women and immunocompromised hosts, the vaccination rate is presumed to be low in pregnant women. This study was aimed to evaluate the vaccination rate and factors associated with Influenza vaccination among pregnant women, who are at high risk for developing complications from the influenza. Materials and Methods:This study was carried out by telephone survey from April, 2007 to August, 2007. Women who were in their second trimester of pregnancy or above,- during October, 2006 and February, 2007, the recommended vaccination period, and had given birth at Inha University Hospital were selected as the study population. Immunization status, general understanding, and factors associated with vaccination were evaluated. Results:Among a total of 506 eligible pregnant women, 227 (44.8%) responded to the questionnaires. The influenza vaccination rate among the pregnant women was only 4% (9/227). Major reasons for not receiving vaccination were first, not awaring the necessity of immunization during pregnancy (48.5%, 110/227) and second, misunderstanding that it is prohibited during pregnancy (36.1%, 82/227). The major factors that influenced the compliance of vaccination were correct understanding and doctor's recommendation on the influenza immunization during pregnancy. Conclusions:The influenza vaccine coverage on pregnant women was very low and the awareness of influenza vaccination during pregnancy in general was inaccurate. Shift in perception is required and this can be achieved by educating the pregnant women on the safety and efficacy of vaccination. In addition, doctors' active encouragement to vaccination is highly recommended. Background:During seasonal influenza epidemics and previous pandemics, pregnant women have been at increased risk for complications related to influenza infection. Although influenza vaccination has been widely recommended to pregnant women and immunocompromised hosts, the vaccination rate is presumed to be low in pregnant women. This study was aimed to evaluate the vaccination rate and factors associated with Influenza vaccination among pregnant women, who are at high risk for developing complications from the influenza. Materials and Methods:This study was carried out by telephone survey from April, 2007 to August, 2007. Women who were in their second trimester of pregnancy or above,- during October, 2006 and February, 2007, the recommended vaccination period, and had given birth at Inha University Hospital were selected as the study population. Immunization status, general understanding, and factors associated with vaccination were evaluated. Results:Among a total of 506 eligible pregnant women, 227 (44.8%) responded to the questionnaires. The influenza vaccination rate among the pregnant women was only 4% (9/227). Major reasons for not receiving vaccination were first, not awaring the necessity of immunization during pregnancy (48.5%, 110/227) and second, misunderstanding that it is prohibited during pregnancy (36.1%, 82/227). The major factors that influenced the compliance of vaccination were correct understanding and doctor's recommendation on the influenza immunization during pregnancy. Conclusions:The influenza vaccine coverage on pregnant women was very low and the awareness of influenza vaccination during pregnancy in general was inaccurate. Shift in perception is required and this can be achieved by educating the pregnant women on the safety and efficacy of vaccination. In addition, doctors' active encouragement to vaccination is highly recommended.

Immunogenicity and safety of a cell culture-derived inactivated trivalent influenza vaccine (NBP607): A randomized, double-blind, multi-center, phase 3 clinical trial

Song, Joon Young,Cheong, Hee Jin,Lee, Jacob,Woo, Heung Jeong,Wie, Seong-Heon,Lee, Jin-Soo,Kim, Shin Woo,Noh, Ji Yun,Choi, Won Suk,Kim, Hun,Kim, Kyung-Ho,Kim, Woo Joo Elsevier 2015 Vaccine Vol.33 No.41

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Cell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity.</P> <P><B>Methods</B></P> <P>A randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (Agrippal<SUP>®</SUP>S1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number—NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination.</P> <P><B>Results</B></P> <P>A total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups.</P> <P><B>Conclusion</B></P> <P>NBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A cell culture-derived influenza vaccine (NBP607) showed excellent long-term immunogenicity. </LI> <LI> NBP607 had tolerable safety profiles with no significant difference compared to the egg-based vaccine. </LI> <LI> NBP607 was more immunogenic against influenza B compared to the egg-based vaccine. </LI> </UL> </P>

Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines

Sang-Hyun Kim,Erica Espano,Bill Thaddeus Padasas,Ju-Ho Son,Jihee Oh,Richard J. Webby,Young-Ran Lee,Chan-Su Park,Jeong-Ki Kim The Korean Association of Immunobiologists 2024 Immune Network Vol.24 No.3

The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

Delayed-Onset Anaphylaxis Caused by IgE Response to Influenza Vaccination

Min Jung Kim,Doo Hee Shim,Hye-Ran Cha,Cheong Bi Kim,Soo Yeon Kim,Jeon Han Park,Myung Hyun Sohn,이재면,김경원 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.2

Influenza vaccine-associated anaphylaxis is a very rare allergic reaction to vaccines, but the most concerning and life-threatening adverse reaction. Although the safety of influenza vaccines has been well documented, occasional cases of anaphylaxis in vaccinated patients have been reported. In this study, we analyzed the immunoglobulin E (IgE) response to whole influenza vaccines in a pediatric case of delayed-onset anaphylaxis after influenza vaccination. The patient showed elevated specific IgE levels against whole influenza vaccines, especially with split virion from egg-based manufacturing process. Specific IgE levels to influenza vaccines showed decreased over. We evaluated a causal relationship between influenza vaccine and anaphylaxis event by enzyme-linked immunosorbent assay. Delayed-onset anaphylaxis after influenza vaccination can occur in children without predisposing allergic diseases. In addition, the results suggested that formulation and production system of influenza vaccines could affect the probability of severe allergic reaction to vaccines.

The Prevalence of and Factors Associated with Influenza Vaccination in Patients with Asthma in Korea

( Sang Hyuk Kim ),( Sungmin Zo ),( Hwasik Jung ),( Saerom Kim ),( Ho Joo Yoon ),( Jang Won Sohn ),( Tae-hyung Kim ),( Sang-heon Kim ),( Ji-yong Moon ),( Dong Won Park ),( Tai Sun Park ),( Hye Yun Park 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Background Patients with asthma are at high risk of hospitalization and death from influenza infection, which Results in an additional burden on the medical system. However, despite the crucial role of influenza vaccination in preventing influenza infection and its complication, detailed epidemiologic data regarding influenza vaccination among patients with asthma is lacking. This study aimed to investigate the rate of influenza vaccination and factors associated with the vaccination in patients with asthma using nationally representative survey data. Methods Among 72,843 participants of the Korea National Health and Nutrition Examination Survey between 2010 and 2019, 760 patients with self-reported physician-diagnosed asthma were included in this study. The outcome was the influenza vaccination rate assessed by questionnaire. Logistic regression analysis was performed to evaluate factors associated with not being vaccinated in patients with asthma. Results The overall influenza vaccination rate was 63.7% in patients with asthma and there was no significant change in the vaccination rate (range 58.7%-70.0%) during the study period. In multivariable logistic regression analysis, younger age (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 1.07-1.16, p < 0.001), lower income (aOR 2.76, 95% CI 0.77-3.80, p = 0.040), and the presence of respiratory symptoms (aOR 2.56, 95% CI 1.22-5.36, p = 0.012) were associated with the increased odds of being unvaccinated for influenza. Conclusion The vaccination rate in patients with asthma was stable, ranging from approximately 60% to 70% between 2010 and 2019 in Korea. As patients with younger age, lower income, or respiratory symptoms might be non-adherent to influenza vaccination, more attention is needed in these patients to increase the influenza vaccination rate. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, Information and Communications Technologies (MSIT) (NRF-2020R1F1A1070468 and NRF-2021M3E5D1A01015176).

50세 이상 천식 환자의 인플루엔자 백신 접종률 및 관련 요인

최보영,변경향 한국학교·지역보건교육학회 2018 한국학교지역보건교육학회지 Vol.19 No.3

Objectives: This study aims to investigate the estimated proportion for influenza vaccination and to identify factors associated with influenza vaccination in Korean adults aged 50 and older with asthma. Methods: Data from 2010-2015 Community Health Survey(n=23,662) was used. A chi-square test was performed to investigate the estimated proportion for influenza vaccination, and a multiple logistic regression analysis was used to identify the factors associated with self-reported influenza vaccination. Results: In men, 42.3-49.5% of asthma patients 50–64 years of age, and 78.5-90.2% of elderly (over 65 years of age) asthma patients received influenza vaccination. In women, 49.7-61.9% of asthma patients 50–64 years of age, and 82.7-89.7% of elderly asthma patients received influenza vaccination(p<0.0001). Low education level, non-smoking, non-drinking, hypertension, diabetes and use of public center were related to high influenza vaccination in 50–64 years old men with asthma. Low education level, non-smoking, bad health status, hypertension, diabetes and use of public center were related to high influenza vaccination in 50–64 years old women with asthma. Non-smoking and use of public center were related to high influenza vaccination in over 65 years old men with asthma. White-collar jobs, smoking, absence of hypertension and use of public center were related to low influenza vaccination in over 65 years old women with asthma. Conclusions: Influenza vaccination remains relatively low in asthma patients 50–64 years of age. It is necessary to recommend vaccination to asthma patients, provide them with information, and devise other strategies to improve vaccination.