Naturally acquired immunity to influenza type A. Lessons from two coexisting subtypes

When the H1N1 subtype of influenza reappeared in the Northern Hemisphere during 1977, after a 20-year absence, it behaved very differently from the H3N2 subtype still in circulation. In Sydney, we studied the incidence of both subtypes of laboratory-proven influenza type A in 287 unvaccinated volunteers whose serum antibody titres were measured before and after each winter, to facilitate the detection of subclinical as well as clinical infection. During a 1977 epidemic, the A/Victoria/3/75 strain of the H3N2 subtype attacked participants of all age groups, whereas during epidemics of 1979 and 1981, the A/USSR/90/77 and A/Brazil/11/78 strains of the H1N1 subtype attacked only subjects born after 1950. The older participants apparently possessed homologous protection, acquired as a result of exposure to H1N1 more than 20 years earlier and not dependent upon strain-specific haemagglutination inhibition antibody.     

Influenza A(H1N1): a widening spectrum?

OBJECTIVE: To study the incidence of H1N1 influenza from 1977 to 1988 in unvaccinated volunteers and the effects of continuing minor antigenic change (antigenic drift) in the virus. DESIGN: Prospective study by a group of general practitioners, backed up by virological findings. PARTICIPANTS: Mainly patients of the general practitioner group, also some doctors and members of staff. There were 287 participants during 1977-1981, and 207 at the end of 1988. INTERVENTION: Any participant deemed to be "at risk" was encouraged to be vaccinated and to withdraw from the study. BACKGROUND: In 1957, H1N1 subtype influenza had been displaced by H2N2 (Asian) subtype. In 1968, H2N2 was displaced by H3N2 (Hong Kong) subtype. During 1977, H1N1 influenza unexpectedly reappeared in Asia, and spread widely. The resurgent strain, designated A/USSR/90/77(H1N1), caused world pandemics, attacking (almost exclusively) persons who had been born since the 1950-1951 northern winter and causing negligible mortality. It did not displace the current H3N2 strain, and strains of both subtypes have continued to emerge independently. HYPOTHESIS: Antigens of A/USSR resembled closely those of the 1950-1951 H1N1 strain, which apparently was rendered antigenically inert between 1951 and 1976 (possibly frozen) and was reactivated during 1977. Antigenic drift was then resumed. MAIN OUTCOME MEASURE: The A/USSR/90/77 strain and its close successor, A/Brazil/11/78, attacked mainly the young, whose previous exposure to H1N1 antigens had been minimal or zero. Mortality during the A/USSR pandemics was negligible because death from influenza in people aged less than 30 years is rare. Would continuing antigenic drift ultimately widen the H1N1 spectrum of attack? RESULT: During the epidemic of 1988, A/Taiwan/1/86(H1N1) attacked a wider range of age groups than had A/USSR or A/Brazil. CONCLUSION: Assuming that H1N1 viruses continue to undergo further antigenic drift, an ever widening age spectrum of H1N1 attack may be expected.     

Age-related responses to influenza vaccination in the Newcastle region during 1983 and 1984

A study was carried out in Newcastle to assess responses to influenza vaccines in elderly nursing home patients and in younger adults during 1983 and 1984. The decision to vaccinate the elderly subjects was made by their general practitioners. A concurrent randomized placebo-controlled trial of the same vaccine was performed in young adult volunteers. Elderly subjects generally possessed higher levels of pre-existing antibody to the influenzal haemagglutinins that were present in the vaccines than did younger subjects. The highest levels were observed in the 52-63 years' age group. Younger subjects showed significantly greater responses to vaccines compared with elderly subjects (P less than 0.05). Peak responses were noted in the 16-24 years' age group. Of a total of 326 elderly subjects (70% of whom had been vaccinated), six participants, two of whom had been vaccinated, contracted laboratory-proven influenza during 1983. Only one unvaccinated subject of a total of 365 subjects (50% of whom had been vaccinated) contracted influenza during 1984. In both years illness was produced by strain A/Philippines/2/82.     

Placebo-controlled double-blind clinical studies on the efficacy of different influenza vaccines assessed by experimental and natural infection

Four placebo-controlled double-blind studies on the protective efficacies of a freeze-dried aerosol and an injectable whole-virion inactivated influenza vaccine, each containing 400 i.u. A/Port Chalmers/1/73 (H₃N₂) and 240 i.u. B/Hong Kong/8/73 per dose, were carried out on a total of 601 subjects using three different live influenza vaccines as challenge virus. In the second of these studies a tween-ether ‘split’ aluminium-absorbed injectable vaccine containing 400 CCA units A/Port Chalmers/1/73 (H₃N₂) and 300 CCA (chick cell agglutination) units B/Hong Kong/8/73 was also tested. Challenge in the first three studies occurred 3 weeks after vaccination whereas in the last study it took place 3 months after vaccination. The live vaccines were recommended for the 1974-75 season in Belgium, Rumania and Yugoslavia in which countries the studies were performed and contained an A/England/42/72 (H₃N₂)-like strain, a B/Victoria/98926/70-like strain and an A/Port Chalmers/1/73 (H₃N₂)-like strain respectively. The latter vaccine was used in both of the last two studies. Infection with the vaccine strain was diagnosed by virus isolation and/or serological response after challenge since this produced negligible clinical signs and symptoms.     

Evidence of prior infection with influenza A/Texas/77 (H3N2( virus in dogs with clinical parainfluenza

Eighty dogs exhibiting clinical signs of respiratory disease were sampled for influenza virus isolation and serologically tested for hemagglutination inhibiting antibody to influenza A/Hong Kong/68, A/Victoria/75, A/Texas/77 and A/USSR/77. Forty-one animals without clinical signs of respiratory disease were also examined serologically. Hemagglutinating agents were isolated from nasal and/or pharyngeal swabs taken from 21 of the 80 dogs with clinical respiratory disease. Twenty of these 21 isolates were canine parainfluenza virus. Twenty-one of 80 clinically ill animals (26.3%) and eight of 41 normal animals (19.5%) had low level hemagglutination inhibiting antibody to influenza A/Texas/77. There was no evidence that human influenza caused the respiratory disease in the dogs included in this study, since none had an increase in hemagglutination inhibiting antibody to influenza in convalescent sera. The presence of antibody to A/Texas/77, however, does suggest the possibility that these dogs had at some time been infected with this virus, and that dogs could play a role in the epidemiology of influenza in man.     

Reye syndrome with associated influenza A and B infection.

In early 1974, seventeen children were treated for Reye syndrome. Thirteen of these were studied for laboratory evidence of concomitant viral infection. Influenza B/Hong Kong was isolated from the pharynx in four of nine 1974 cases tested. One child had just recovered from varicella. Adenovirus type 2 and respiratory syncytial virus were isolated from two additional patients. Serologic tests for influenza suggested concomitant or recent influenza B infection in ten of 13 of 1971 cases. During February 1975, six children were treated for this syndrome. Influenza A/Port Chalmers was recovered from three in six 1975 cases, and all six showed significant antibody rises to influenza A. These studies suggest that influenza viruses provide a trigger mechanism for the development of Reye syndrome in susceptible children.     

Use of temperature-sensitive mutants of influenza A virus as live virus vaccine strains. Evaluation in laboratory animals, adults and children

Temperature-sensitive (ts) recombinants of influenza A virus were evaluated for use in a live virus vaccine. Evidence from several sources suggested that the ts lesions were responsible for attenuation of these mutants. Specification of attenuation by defined genetic lesions which can be assayed for in the laboratory offers an advantage to the use of ts viruses for vaccination. This means that ts recombinants can be assessed for genetic stability during vaccine development, production and later during usage in man. One ts virus, influenza A/Hong Kong/68-ts-1[E], with a 38°C shut-off temperature, had the following properties desirable for a live virus vaccine: (1) satisfactory infectivity for seronegative (serum HI antibody titre ≤ 1:8) adults; (2) satisfactory attenuation for adults; (3) capacity to stimulate local and serum anti-haemagglutinin and anti-neuraminidase antibodies in seronegative volunteers; (4) stimulation of resistance to virulent, wild type virus; (5) relative genetic stability in vivo; (6) lack of communicability in man; (7) replication to high titre in avian leucosis virus-free eggs; and (8) localization of ts lesions to genes that do not code for the haemagglutinin and neuraminidase. The ts lesions of influenza A/Hong Kong/68-ts-1[E] virus were transferred to more current viruses within the H₃N₂ subtype (influenza A/Udorn/307/72 and influenza A/Georgia/101/74). These recombinant Udorn/72 and Georgia/74 ts viruses, which possessed the same shut-off temperature and the same ts lesions as the influenza A/Hong Kong/68-ts-1[E] parent virus, exhibited a pattern of infection and attenuation in hamsters and man similar to their ts parent. These data suggest that ts mutants which are sufficiently attenuated for man, could serve as donors of ts lesions for the rapid production of an attenuated vaccine when new antigenic variants arise.     

广州市某区2008年度流行性感冒的流行情况调查

目的了解广州市某区2008年度流感发病及抗原变异情况,为制定流感防治策略提供科学依据。方法利用流感监测点定期采集的流感样标本,以MDCK细胞分离病毒,并应用红细胞凝集抑制法进行型别鉴定,对流感的病原学以及流感疫情监测情况进行统计分析。结果全年共监测咽拭子763份,分离病毒株80株,其中A（H1N1）型37株,A（H3N2）14株,B（Victoria）23株,B（Yamagata）6株。15岁以下人群发病最多,占流感样病例的65．00％。全年发生流感疫情2起。春季以B（Victofia）为主,夏季以A（H1N1）为主。结论全年广州市某区流感发病呈散发,并以H1N1亚型为主,15岁以下人群为流感高危人群,流感发病高峰出现在3月份和7月份。     

2010—2012年深圳市龙岗区流感病原学监测分析

目的分析2010-2012年深圳市龙岗区流感流行特点和流感病毒优势株的情况。方法对区内监测哨点流感标本进行狗肾传代细胞（MDCK）病毒分离与血凝试验鉴定,描述性分析区内流感的流行情况。选取B型流感优势病毒株进行RT-PCR扩增HA1片段并测序。测序结果与WHO流感疫苗株进行同源性比对,绘制系统发生树。结果2010—2012年共采集流感样病例咽拭子1014份,流感病毒分离率为30．6％（310／1014）,其中新甲型H1N1亚型80株（25．8％）,季节性H1N1亚型I株（0．3％）,季节性H3N2亚型85株（27．5％）,B型流感Victoria亚型138株（44．5％）,Yamagata亚型6株（1．9％）。不同年龄组病毒阳性率差异有统计学意义（X^2=21．194,P〈0．05）,以25-岁年龄组阳性率（35．5％）最高。2010—2012年龙岗区流感优势流行株依次为B型流感Victoria型、新甲H1N1型、甲型H3N2型。系统进化树显示2013年WHO推荐流感疫苗与本区流感病毒同处一个分支。结论龙岗区同时存在多种流感病毒交替流行现象,但新预测流感疫苗可有效覆盖本区流感病毒。     

中国2009年甲型H1N1流感病毒进化分析

目的研究2009年中国甲型H1N1流感病毒的进化特性和变异情况,为甲型H1N1流感的监控和防治提供科学依据。方法利用ClustaX进行序列比对,以Bioedit软件进行序列同源性分析,使用Mega 4.0软件采用邻位相连算法构建进化树,对2009年登录在Genbank数据库中的中国甲型H1N1流感病毒的HA、NA、M蛋白的氨基酸序列进行系统进化分析。结果中国2009年甲型H1N1流感病毒分离株与美国分离株[A/California/04/2009（H1N1）]具有很近的亲缘关系,不同省份分离株之间的HA、NA、M蛋白相互交叉渗透,但同时各个省份间暴发的H1N1流感病毒的HA蛋白又具有一定的聚集性。香港分离株[A/Hong Kong/2369/2009（H1N1）]和上海分离株[A/Shanghai/LWS1/2009（H1N1）]产生了对达菲的耐药性,其他毒株仍然敏感;上海分离株[A/Shanghai/LWS1/2009（H1N1）]对金刚烷胺类药物敏感,其余毒株均对其耐药。结论本研究表明,中国2009年甲型H1N1流感病毒不仅具有很强的保守性,同时又具有一定的区域特异性,毒株相对稳定,没有出现大的变异。     

2006～2007年泰安市流感病毒检测结果分析

目的对2006—2007年度泰安市流行性感冒的病原学监测结果进行分析，了解泰安市流感流行情况，为流感防治提供科学依据。方法采集流感样病例（ILI）的咽拭子标本，用狗肾细胞（MDCK）进行病毒分离，采用血凝抑制方法（HAI）进行流感病毒型别鉴定。结果检测的国家级流感监测医院ILI咽拭子标本243份，分离到流感病毒25株，阳性分离率为10．29％，经分型鉴定A（H3N2）亚型14株，A（H1N1）亚型1株，B型Victoria系10株；结论2006～2007年度泰安市有流感流行，流行的优势毒株为A（H3N2）亚型和B型Victoria系，同时有A（H1N1）亚型毒株的存在，B型Victoria系主要在幼儿中流行。     

中国甲型流感病毒血凝素基因进化分析

目的 探索甲型流感的暴发规律及毒株血凝素（hemagglutinin,HA）基因的进化.方法 通过分析中国采集并公布的甲型流感病毒基因数据,对中国大陆所有宿主为人、禽类和哺乳动物的HA基因氨基酸序列进行多序列比对,并用于构建HA的系统发育树,同时对中国香港地区的HA基因蛋白序列同样处理;分析不同宿主的HA基因的受选择压力.结果 选择中国大陆1 252个HA基因和香港485个HA基因,对其分析发现,自2002年以来,禽流感的暴发次数和频率多于历史记录;系统发育树结果显示中国大陆和香港地的HA基因邻接树的拓扑结构一致;宿主为人的HA基因受选择大于禽类宿主的HA基因.结论 不同宿主的HA基因受选择有差异,提示HA基因的快速进化可能会对人类健康产生潜在威胁.     

Effect of influenza on cardiorespiratory and all-cause mortality in Hong Kong, Singapore and Guangzhou

1. Using a common modelling approach, mortality attributable to influenza was higher in the two subtropical cities Guangzhou and Hong Kong than in the tropical city Singapore. 2. The virus activity appeared more synchronised in subtropical cities, whereas seasonality of influenza tended to be less marked in the tropical city. 3. High temperature was associated with increased mortality after influenza infection in Hong Kong, whereas relative humidity was an effect modifier for influenza in Guangzhou. No effect modification was found for Singapore. 4. Seasonal and environmental factors probably play a more important role than socioeconomic factors in regulating seasonality and disease burden of influenza. Further studies are needed in identifying the mechanism behind the regulatory role of environmental factors.     

Inactivated influenza vaccines. 2. Laboratory indices of protection

The data from our 1968-69 influenza vaccine field trials are anlaysed and pre-challenge haemagglutinin and neuraminidase serum antibodies are evaluated as indices of protection. Prevention of flu-like disease, fever, confinement to bed, and/or seroconversion to Hong Kong was significantly related to post-vaccine A/Hong Kong/68(H3N2) haemagglutination-inhibition (HI) titres. Prevention of disease was also related, although not significantly statistically in every category, to pre-challenge A/Hong Kong/68 neuraminidase inhibition (NI) titres. The trend was the same regardless of whether the origin of the NI antibody was through A/Aichi/68 or A/Japan/62 vaccines or through pre-Hong Kong influenza infections. In summarizing the data using fever as an index of disease, the attack rate (AR) among volunteers without Hong Kong NI or HI antibody was 45%. Presence of NI antibody, in the absence of HI antibody, significantly reduced the AR to 24%. Those with both NI and HI titres experienced a still lower AR of 14%. Those with HI and NI titres both > 1: 160 ran little risk of disease, with an AR of 7%.     

2011～2013年吉安市流感监测分析与防控对策

目的：分析吉安市2011～2013年流感流行特征及流感病毒毒株型别,为流感防控提供科学依据。方法通过中国流感监测信息系统,收集2011～2013年吉安市流感样病例资料进行统计分析。采集流感样病例咽拭子标本用聚合酶链反应（PCR）法检测流感病毒核酸,并鉴定型别。结果2011～2013年吉安市流感样病例主要集中在25～60岁的中青年,其次为5～15岁的少年;发病高峰在9、11、1、2月。2011～2013年共检测流感样病例标本1715例,阳性标本340例,阳性率19.8%。2011年1月～2011年3月流感以新甲H 1N 1与B型并存,2012年年初以B型为主,5～7月转为季H 3为主,2013年年底以季H3为主,并伴随有B型。结论吉安市流感发病高危人群是中青年,且具有一定的季节性,以冬春季节发病较多。流感病毒存在新甲H1N1、季H3和B型交替感染的现象,应加强监测和采取各项针对性的预防措施,有效控制流感的发生。     

Nasal and circulating antibody responses to influenza vaccination and their importance in resistance to infection

Small groups of volunteers were inoculated intranasally with live-attenuated, and parenterally with detergent-split-saline or with whole-virus-oil-adjuvant influenza A2/HK (H3N2) vaccines after the prevalence of Hong Kong strains. Antibody titres in nasal secretions and serum were measured by HI, antineuraminidase and neutralization tests. The oil adjuvant vaccine produced large rises in antibodies and the other two vaccines produced small rises. The volunteers given oil adjuvant and live vaccine were both well protected against challenge with a partly attenuated strain. Statistical analysis showed that resistance to infection was predicted best by high titres of antibody in the serum, but the presence of antibody did not seem to explain completely resistance to infection.     

乌鲁木齐市2011-2012年度流感监测结果分析

目的对乌鲁木齐市流感监测结果进行分析,了解乌鲁木齐市流感流行动态,为流感防治提供科学依据。方法对2011年4月-2012年3月间乌鲁木齐市哨点医院的流感样病例(influenza-like illness,ILI)资料、流感疫情资料和病原学监测结果进行分析。结果 2011-2012年度全市哨点医院共报告流感样病例(ILI)27 848例,流感样病例就诊百分比(ILI%)平均为10.75%(27 848/259 062)。共采集流感样病例标本977份,核酸检测阳性148份,阳性率15.15%,其中B型104份、新甲型H1N1型22份、H3N2亚型21份、混合型1份。分离出流感病毒31株,分离率20.95%(31/148),以季节性流感B型为主,占64.52%。结论乌鲁木齐市2011-2012年度季节性流感高峰在1-3月,以B型流感病毒为主,H3亚型和新甲型H1N1亚型混合流行。加强流感的实时监测和及易感人群的防护,对我市流感的防控工作具有重要意义。     

2012-2013年石家庄市流行性感冒监测结果分析

目的分析石家庄市流行性感冒（简称流感）流行病学特征,为流感的防控提供参考依据。方法收集2012年4月-2013年3月石家庄市流感样病例的监测数据,分析流行病学及病原学检测结果。结果 2012-2013年石家庄市流感监测哨点医院流感样病例（influenza-like illness,ILI）就诊百分比（ILI%）平均为1.05%,冬春季节出现流行高峰。共采集流感样病例标本711份,核酸检测阳性108份,阳性率为15.18%。分离得到流感毒株92株,总分离率为12.94%,其中B型1份、甲型H1N1型47份、季节性H3N2型44份。结论石家庄市流感活动具有季节性特点,活动高峰期出现在冬春季节,ILI流行高峰与病毒检出高峰基本一致。季节性H3N2型流感毒株在2013年1月前为主要优势流行株,2013年1月后甲型H1N1型流感毒株成为优势流行株。病毒分离率与年龄及性别无关。     

河池市2010～2012年散发流感样病例监测分析

目的 了解河池市人群散发流感样病例流感病毒感染状况、毒株型别及流行特征.方法 2010～ 2012年对就诊的散发流感样病例进行调查和采集咽拭子标本,采用实时荧光定量RT-PCR对标本进行流感病毒核酸检测.结果 2010～2012年共调查流感样病1 115例,流感病毒感染166例,平均感染率为14.89％(9.98％～25.58％),病毒毒株为季节性甲型H3亚型、乙型和甲型H1N1亚型.流感病毒感染率高峰分别为1～3月和6～7月.男女性别感染率差异无统计学意义(P＞0.25);15岁以下人群感染率较低(P＜0.05),与流感疫苗接种率较高有关;流感病毒感染病例中,以干部职员、学生和农民为多.结论 河池市人群流感病毒感染呈现两个高峰,应采取包括流感疫苗预防接种在内的有效防控工作.     

惠州市流感病原学监测结果分析

目的对我市流感样病例标本进行病原学检测,分析其病原学特点,为流感防控提供病原学依据。方法采用MDCK细胞(狗肾细胞)培养法分离流感病毒,用血凝抑制试验对病毒株进行分型鉴定。结果从哨点医院采集的520份标本中共分离出流感病毒41株,分离率为7.9%,以新甲型H1N1为主。其中新甲型H1N126株(63.4%),H3N2型5株(12.2%),B(Yamagata)型1株(2.4%),B(Victoria)型9株(22.0%)。流感流行高峰出现在春季的1-3月和秋季的8-9月。健康人群血清中流感抗体的阳性率不高,最高为新甲型H1N1抗体阳性率41.9%,最低为B(Yamagata)的抗体阳性率,仅8.1%。对2010年2株新甲型H1N1进行基因测序,结果显示甲型H1N1基因未发生变异,暂时不会造成大的流行。结论惠州市流感病毒的流行时间有明显的季节性,活动相对平缓,新甲型H1N1流感病毒是春季的优势毒株,下半年逐渐转变为H3N2型流感病毒。