H5N1 vaccines in humans

The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemic spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective and long-lasting responses, that can be administered as soon as a pandemic is declared or possibly even before, in order to prime the population and allow for a rapid and protective antibody response. In the last few years, several vaccine manufacturers have developed candidate pandemic and pre-pandemic vaccines, based on reverse genetics and have improved the immunogenicity by formulating these vaccines with different adjuvants. Some of the important and consistent observations from clinical studies with H5N1 vaccines are as follows: two doses of inactivated vaccine are generally necessary to elicit the level of immunity required to meet licensure criteria, less antigen can be used if an oil-in-water adjuvant is included, in general antibody titers decline rapidly but can be boosted with additional doses of vaccine and if high titers of antibody are elicited, cross-reactivity against other clades is observed. Prime-boost strategies elicit a more robust immune response. In this review, we discuss data from clinical trials with a variety of H5N1 influenza vaccines. We also describe studies conducted in animal models to explore the possibility of reassortment between pandemic live attenuated vaccine candidates and seasonal influenza viruses, since this is an important consideration for the use of live vaccines in a pandemic setting.     

COVID-19 vaccination: The impact on the selection criteria of the convalescent plasma donors

Clinical management protocols for COVID-19 are evolving rapidly as more information about the epidemiology and pathophysiological changes in COVID-19 become available. However, no definite treatment of COVID-19 has been found till date. The COVID-19 convalescent plasma (CCP) therapy has emerged as an important investigational therapy in the management of COVID-19 patients. Additionally, the regulatory agencies, in particular, the Indian blood transfusion council must release some interim recommendations for the blood centres on the CCP blood donor eligibility criteria after COVID-19 vaccination. More clinical trials are needed to know the efficacy of the CCP harvested from COVID-19 recovered individuals who have been vaccinated against those COVID-19 recovered individuals who are not vaccinated to understand the vaccine impact on the IgG titres of anti-SARS-CoV-2 antibodies.     

The Development and Operation of a Home Management System during the COVID-19 Pandemic: Experience of the Local Government Gyeonggi-do in Korea

During the three the coronavirus disease 2019 (COVID-19) surges in South Korea, there was a shortage of hospital beds for COVID-19 patients, and as a result, there were cases of death while waiting for hospitalization. To minimize the risk of death and to allow those confirmed with COVID-19 to safely wait for hospitalization at home, the local government of Gyeonggi-do in South Korea developed a novel home management system (HMS). The HMS team, comprised of doctors and nurses, was organized to operate HMS. HMS provided a two-way channel for the taskforce and patients to monitor the severity of patient''s condition and to provide healthcare counseling as needed. In addition, the HMS team cooperated with a triage/bed assignment team to expedite the response in case of an emergency, and managed a database of severity for real-time monitoring of patients. The HMS became operational for the first time in August 2020, initially managing only 181 patients; it currently manages a total of 3,707 patients. The HMS supplemented the government''s COVID-19 confirmed case management framework by managing patients waiting at home for hospitalization due to lack of hospital and residential treatment center beds. HMS also could contribute a sense of psychological stability in patients and prevented the situation from worsening by efficient management of hospital beds and reduction of workloads on public healthcare centers. To stabilize and improve the management of COVID-19 confirmed cases, governments should organically develop self-treatment and HMS, and implement a decisive division of roles within the local governments.     

Influenza: forecast for a pandemic

Recently, great speculation about a possible influenza pandemic has been made. However, the facts supporting the possibility of this threat are less discussed. During the last decade highly pathogenic strains of avian influenza virus, including the H5N1 subtype, crossed the species barriers from birds to humans and caused fatal disease. The Z strain of H5N1 subtype is characterized by pathogenicity to a larger number of animal species and by resistance to the older class of antiviral drugs. At present, two out of three general conditions for the onset of a pandemic have been met; namely, the emergence of a new virus and its ability to replicate in humans causing serious illness. Should the virus achieve efficient human-to-human transmission, the next influenza pandemic might occur. This review addresses these biological and epidemiological aspects of influenza in the context of history and characteristics of previous epidemics, as well as concrete actions that can be undertaken considering current understanding of influenza pathogenesis, treatment, and control possibilities.     

Anticipating crisis: towards a pandemic flu vaccination strategy through alignment of public health and industrial policy

Flu pandemics (worldwide epidemics) have occurred at irregular and unpredictable intervals, and have been associated with substantial morbidity, mortality and economic cost. In response to the emerging potential for a new pandemic to occur, national and international preparedness plans are being drawn up specifying the use of antivirals and vaccines. A number of challenges to pandemic vaccine development, large-scale production and the timing of distribution have also been highlighted. This article reviews the rationale and consequential policy for aligned public- and private sector planning in the present inter-pandemic period despite the prevalent risks and uncertainties. We propose a model for product development of pandemic flu vaccine based on public–private partnership, including push and pull incentive mechanisms for stimulating work in this therapeutic area. In addition, we argue that innovative vaccination strategies, together with special vaccine formulations which may offer cross-protection against multiple flu pandemic strains might avert the worse effects of an influenza infection.     

赣州市2014年新型甲型H1N1流感病毒NA基因特征及耐药性分析

目的：分析江西省赣州市2014年新型甲型H1N1流感病毒NA基因的特点,掌握其耐药情况,为临床治疗和疾病控制提供参考依据。方法随机选择17株新型甲型H1N1流感病毒,经核酸提取和one-step RT-PCR扩增NA基因片段,双向序列测定,采用DNAStar5.0和Mage4.0序列分析软件分析NA基因特征以及耐药性位点。结果17株毒株的NA基因片段与代表株A/California/07/2009(H1N1)的序列核苷酸序列进行比对,核苷酸序列同源性高达98.4%以上,氨基酸的同源性也高达97.0%以上。17株毒株的NA活性中心位点氨基酸及周围的辅助位点氨基酸均未发生氨基酸替换。结论17株毒株的NA基因片段保持高度的同源性并均对流感病毒神经氨酸酶抑制剂药物敏感,但仍应加强对流感病毒的耐药性监测,为制定新型甲型H1N1流感的防制措施提供技术支持。     

Attendance and vaccination at immunization clinics in rural Gambia before and during the COVID-19 pandemic

IntroductionThe COVID-19 pandemic has affected the delivery of essential health services, such as routine immunization. We assessed the impact of the pandemic on the uptake of routine immunization in rural Gambia.MethodsWe collected real-time vaccine administration data in the Basse and Fuladu West Health & Demographic Surveillance Systems from September 01, 2019, to December 31, 2020. We assessed the monthly number of Expanded Program on Immunization (EPI) clinic attendances and vaccines administered, comparing data during the baseline period (September 01, 2019–March 31, 2020), COVID-19 interruption period (April 01–June 30, 2020), initial recovery period (Jul 01–September 30, 2020) and the late recovery period (October 01–December 31, 2020).ResultsCompared to the baseline period, there was an overall average monthly decline of 13.4% in EPI attendance and 38.3% reduction in average monthly immunizations during the interruption period. This decrease was particularly noticeable for Bacille Calmette-Guérin (BCG) (47.2%), birth dose hepatitis B (Hep B) (46.9%), 1st dose pentavalent (Penta1) (43.1%), 1st dose pneumococcal conjugate vaccine (PCV1) (42.4%), and measles vaccines (15.5%). Comparing the late recovery to baseline period, average monthly EPI attendance was 5.3% higher, with 1.9% increase in average monthly immunizations. Monthly immunizations for BCG were 3.0% greater, 2.5% greater for Hep B, 22.7% greater for oral polio vaccine (OPV1), 2.0% less for Penta1, 19.2% less for Penta2, and 2.6% less for PCV1.ConclusionThe reduced EPI attendance during the pandemic interruption period lasted only 3 months. Significant recovery in EPI attendance occurred during the late recovery period, while rates of monthly immunization returned to pre-pandemic levels for most antigens. EPI programmes should implement strategies to deliver missed antigens when infants do present to EPI clinics, aware that missed doses may be age dependent.     

Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

Background

Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.

Methods

An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18–59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed.

Results

A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008–09 or 2009–10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000–01 to 2006–07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever.

Conclusions

A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.