신종인플루엔자 대유행 대비 면역 특성분석을 통한 예방효과 예측연구

초록

연구목표 ○ 신·변종 인플루엔자 유행 대비 계절인플루엔자 백신 접종자의 국내 유행 고병원성 조류인플루엔자 교차 중화능 평가로 예방효과 및 발생 위험 평가 연구내용 및 결과 1. 계절인플루엔자 백신주 및 국내외 조류인플루엔자 바이러스 분리주 확보1) 계절인플루엔자 백신주 4종(H1N1, H3N2, B/Victoria, B/Yamagata) 확보2) 저병원성 및 고병원성 조류인플루엔자 바이러스 분리주 12종 확보 2. 인플루엔자 바이러스에 대한 중화능 시험법 확립 1) 계절인플루엔자 바이러스 및 조류인플루엔자 바이러스 배양 및 역가 측정 2) 중화능 시험법(HI assay, MN assay, PRNT) 확립 및 표준작업지침서(SOP) 개발3. 계절인플루엔자 백신 접종자 검체 수집 1) 연구대상자 선정(고령층, 요양병원 종사자, AI 대응요원, 연구활동종사자) 및 검체 수집 체계 확보 2) 검체 수집을 위한 생명윤리심의위원회(IRB) 심의 3) 연구대상자 대상 백신 접종 전, 접종 후 1, 6, 10개월 검체 수집 4. 계절인플루엔자 백신 접종자 대상 조류인플루엔자 바이러스에 대한 교차 중화능 평가 1) 백신주 4종 및 국내 인체감염 발생위험이 높은 혈청형 6종에 대한 HI assay, MN assay 역가 측정 및 분석 2) 조류인플루엔자 바이러스에 대해 일부 비특이적인 반응을 보였으나, 충분한 교차 방어효과는 보이지 않았음 3) 계절인플루엔자 백신주에 대한 항체 역가는 백신 접종 여부에 따라 유의하게 증가, 6개월 시점에는 유의하게 감소함 기대효과 및 활용방안 ○ 「신종 인플루엔자 대유행 대비·대응 계획」에 따라 조류인플루엔자 인체 감염증 발생 시 예방효과 및 유행 예측을 위한 기초자료로 활용 ○ 신·변종 인플루엔자 유행 대비 신속 백신 개발을 위한 인프라(검사법, 병원체 등)를 확보, 제공

Influenza viruses are characterized by frequent antigenic variation, which increases the likelihood of the emergence of novel strains; consequently, highly pathogenic avian influenza virus (HPAI), particularly the H5N1 subtype, has been continuously identified as a leading candidate pathogen for the next pandemic. Although no human cases of HPAI infection have been reported in Korea to date, the recent detection of infections in wild mammals indicates a persistent risk of human transmission, underscoring the need for preparedness. Four seasonal influenza vaccine strains for the 2023–2024 season were secured from the National Institute for Biological Standards and Control (NIBSC). For avian influenza viruses, a total of seven domestic low- and highly pathogenic avian influenza virus isolates were obtained through the Korea Veterinary Culture Collection (KVCC), and five overseas low- and highly pathogenic isolates were acquired from BEI Resources. Using the secured virus strains, conditions for influenza virus neutralization assays, including hemagglutination inhibition (HI), microneutralization (MN), and plaque reduction neutralization tests (PRNT), were established. The finalized assay protocols were documented as standard operating procedures (SOPs) and will be utilized and provided for future research, including vaccine development. Serum samples were collected before vaccination and at 1 and 6 months post-vaccination from elderly residents aged ≥65 years in long-term care facilities, healthcare workers in these facilities, avian influenza response personnel, and laboratory researchers. These groups were selected as priority vaccination populations during an influenza pandemic to generate evidence supporting infection control measures and vaccination policies for high-risk populations. Participants with complete sample sets at all three time points were included: 20 vaccinated and 10 unvaccinated long-term care facility residents, 20 facility workers, and 20 AI response personnel and researchers. Neutralizing antibody responses were analyzed using the established HI assay against four seasonal influenza vaccine strains and six avian influenza virus serotypes with high potential for domestic occurrence and human infection. Antibody titers against seasonal influenza vaccine strains increased significantly following vaccination and declined significantly by 6 months post-vaccination. In contrast, only limited nonspecific responses were observed against avian influenza viruses, with no evidence of sufficient cross-protective immunity. In the vaccinated group, eight individuals showed seropositivity to H9N2-Y280, of whom five met the protective antibody threshold; however, only one case demonstrated seroconversion attributable to vaccination, suggesting that these responses were not vaccine-induced. Additionally, 20% of AI response personnel and researchers exhibited antibody titers above the protective threshold against H9N2-Y280. In conclusion, seasonal influenza vaccine alone does not provide sufficient protection against avian influenza viruses, particularly in elderly populations, exhibited lower antibody titers even against vaccine strains. Therefore, routine influenza vaccination should be strongly recommended to reduce the risk of infection and to enhance preparedness for future influenza pandemics.