Non-vaccinated Populations Research Articles

Geospatial analysis of contagious infection growth and cross-boundary transmission in non-vaccinated districts of North-East Indian states during the COVID-19 pandemic

During the initial phase of the COVID-19 pandemic, the Government of India implemented a nationwide lockdown, sealing borders across states and districts. The northeastern region of India, surrounded by three international borders and connected to mainland India by a narrow passage, faced particular isolation. This isolation resulted in these states forming a relatively closed population. Consequently, the availability of population-based data from Indian Council of Medical Research, tracked through national identification cards, offered a distinctive opportunity to understand the spread of the virus among non-vaccinated and non-exposed populations. This research leverages this dataset to comprehend the repercussions within isolated populations. The inter-district variability was visualized using geospatial analysis. The patterns do not follow any established grounded theories on disease spread. Out of 7.1 million total data weekly 0.35 million COVID-19-positive northeast data was taken from April 2020 to February 2021 including "date, test result, population density, area, latitude, longitude, district, and state" to identify the spread pattern using a modified reaction-diffusion model (MRD-Model) and Geographic Information System. The analysis of the closed population group revealed an initial uneven yet rapidly expanding geographical spread characterized by a high diffusion rate α approximately 0.4503 and a lower reaction rate β approximately 0.0256, which indicated a slower growth trajectory of case numbers rather than exponential escalation. In the latter stages, COVID-19 incidence reached zero in numerous districts, while in others, the reported cases did not exceed100. The MRD-Model effectively captured the disease transmission dynamics in the abovementioned setting. This enhanced understanding of COVID-19 spread in remote, isolated regions provided by the MRD modelling framework can guide targeted public health strategies for similar isolated areas. This study is Funded by Indian Council of Medical Research (ICMR).

Investigation and analysis on the detection of IgG antibodies against the rubella virus among rural childbearing-age women in preconception period in Yunnan Province from 2013 to 2019

A study was conducted on rural women of childbearing age aged 20-49 who underwent the National Free Preconception Health Examination Project (NFPHEP)in Yunnan Province from 2013 to 2019. Descriptive analysis was conducted to determine the negative rate of IgG antibodies against the rubella virus and its differences among various socio-demographic characteristics. Among the 1 511 203 study subjects, the negative rate of IgG antibodies against the rubella virus was 24.36%. Only 2.64% of the population had received rubella virus vaccine. The negative rate of IgG antibodies among rural childbearing-age women in the preconception period in Yunnan Province decreased with age and educational level (Ptrend<0.001). The negative rate of IgG antibodies in ethnic minority women of childbearing age in the preconception period (25.19%) was higher than that of Han women (23.88%). Among the 22 ethnic groups with over 1 000 participants, the negative rates of IgG antibodies in women of childbearing age from the Blang (32.85%), Bouyei (31.03%), Zhuang (31.01%), and Miao (30.70%) ethnic groups were higher than those of women from other ethnic groups. Among the 16 states (cities) in Yunnan Province, the negative rate of IgG antibodies in pregnant women of childbearing age in Wenshan Zhuang and Miao Autonomous Prefecture (38.06%) and Lincang City (32.63%) was higher than that in other states (cities). The negative rate of serum IgG antibodies in women who reported having received rubella virus vaccine (18.60%) was lower than that in other non-vaccinated populations (24.52%). The proportion of rural women of childbearing age in Yunnan Province who were susceptible to the rubella virus before pregnancy was still high. It is necessary to promote rubella vaccination among people susceptible to rubella, especially pregnant women, to prevent rubella virus infection and reduce the incidence rate and disease burden of rubella people.

Clinical, epidemiological, and molecular investigation of Kyasanur forest disease from Karnataka state, India during 2018-2019

Background In this study, we carried out an investigation of Kyasanur Forest Disease (KFD) suspected human cases reported in Karnataka state, India from December 2018 to June 2019. Methods The clinical samples of KFD suspected cases (n = 1955) from 14 districts of Karnataka were tested for KFD using real-time RT-PCR and IgM ELISA. Further, the KFD-negative samples were tested for IgM antibodies against dengue and chikungunya viruses. Monkey samples (n = 276) and tick pools (n = 11582) were also screened using real-time RT-PCR. KFD-positive samples were further analysed using next-generation sequencing along with clinico-epidemiological analysis. Results Of all, 173 (8.8%) cases tested positive for KFD either by real-time RT-PCR (n = 124), IgM ELISA (n = 53) or both tests (n = 4) from seven districts. Among KFD-negative cases, IgM antibody positivity was observed for dengue (2.6%), chikungunya (5.8%), dengue and chikungunya coinfection (3.7%). KFD cases peaked in January 2019 with fever, conjunctivitis, and myalgia as the predominant symptoms and a mortality of 4.6%. Among confirmed cases, 41% received a single dose and 20% received two doses of the KFD vaccine. Of the seven districts with KFDV positivity, Shivamogga and Hassan districts reported KFD viral RNA positivity in humans, monkeys, and ticks. Sequencing analysis of 2019 cases demonstrated a difference of less than 1.5% amino acid compared to prototype KFDV. Conclusion Although the KFD has been endemic in many districts of Karnataka state, our study confirms the presence of KFDV for the first time in two new districts, i.e. Hassan and Mysore. A comparative analysis of KFDV infection among the KFD-vaccinated and non-vaccinated populations demonstrated an insignificant difference.

The Impact of COVID-19 Vaccination on Bulgarian Patients with Uncomplicated Type 2 Diabetes Mellitus as the Only Chronic Condition

Abstract Objective: This retrospective study aimed to investigate the impact of COVID-19 vaccination on Bulgarian patient cohorts with uncomplicated diabetes mellitus type 2 as the only documented chronic comorbidity. We conducted a comparison of fully vaccinated and non-vaccinated populations, considering gender, age groups and vaccine type, across ambulatory, hospital, and ICU settings. Design: Between March 2020 and June 2022, a comprehensive retrospective analysis was conducted on a national level, utilizing data from the Ministry of Health of the Republic of Bulgaria database obtained after a formal written request. The study included a total of 1,126,946 confirmed COVID-19 patients. Results: Among the 1,126,946 confirmed COVID-19 patients, 3,792 individuals (0.33% of the total confirmed cases) had diabetes mellitus as a single chronic condition. Among the 247,441 hospitalized COVID-19 cases, 1,382 patients (0.56% of the total) had type 2 diabetes mellitus. Notably, the majority of patients requiring hospitalization due to supplemental oxygen requirement were unvaccinated women aged between 60 and 69, accounting for 240 patients. The highest mortality rates were observed in both unvaccinated men and women aged between 70 and 79, with 88 patients in each group. Statistical analysis revealed significant findings in favor of reduced rates of ambulatory care [OR = 0.76 (95% CI 0.6471 to 0.8891); p = 0.0006], intensive care admission [OR = 0.38 (95% CI 0.2698 to 0.5282); p &lt; 0.0001], in-hospital mortality [OR = 0.18 (95% CI 0.0864 to 0.3604); p &lt; 0.0001], and ICU-related mortality [OR = 0.17 (95% CI 0.0893 to 0.3436); p &lt; 0.0001]. The vaccinated cohorts who received BNT162b2 demonstrated the lowest observed death rates, with 9 deaths out of 485 individuals (1.8%) across all age groups. Conclusion: In conclusion, this retrospective analysis indicates reduced mortality in patients with uncomplicated type II diabetes mellitus who received vaccination against SARS-CoV-2. Vaccinated individuals also showed significant reduction in ICU admissions.

Nationwide analysis of the impact of COVID-19 in patients with a cardiovascular, oncological or chronic pulmonary disease in the context of an Eastern European country with a low vaccination rate, Bulgaria: March 2020–April 2022

ObjectiveThis study focused on Bulgarian patient cohorts harbouring a single documented chronic comorbidity–cardiovascular pathology, an oncological disease or a chronic pulmonary diseases (CPD) comparing the outcomes in fully vaccinated and...

Vaccination against Varicella Zoster Virus Infection in Less Developed Regions of Guangdong, China: A Cross-Sectional Serosurveillance Study.

Vaccination is the key to prevent varicella zoster virus (VZV) infection in children. Voluntary and self-funded strategies have led to variable vaccination rates against VZV in China. For low-income populations, in particular, the effects of VZV vaccination have been insufficiently estimated. Community-based serosurveillance was conducted in two less developed regions, Zhanjiang and Heyuan, of Guangdong, China. Anti-VZV IgG antibodies in serum were detected by ELISA. The vaccination data were derived from the Guangdong Immune Planning Information System. A total of 4221 participants were involved, of which 3377 were from three counties of Zhanjiang and the other 844 were from one county of Heyuan, Guangdong, China. The total VZV IgG seropositivity rate in vaccinated individuals was 34.30% and 42.76%, while it was 89.61% and 91.62% in non-vaccinated populations of Zhanjiang and Heyuan, respectively. The seropositivity rate increased gradually with age, reaching ~90% in the >20- to 30-year-old group. The VarV vaccination rates of children aged 1-14 years were 60.47% for one dose and 6.20% for two doses in Zhanjiang, and 52.24% for one dose and 4.48% for two doses in Heyuan. Compared with the non-vaccinated group (31.19%) and one-dose group (35.47%), the positivity rate of anti-VZV IgG antibodies was significantly higher in the two-dose group (67.86%). Before the VarV policy was reformed, the anti-VZV IgG positivity rate was 27.85% in the one-dose-vaccinated participants, which increased to 30.43% after October 2017. The high seroprevalence in participants was due to infection of VZV in Zhanjiang and Heyuan, not vaccination against VZV. Children aged 0-5 years are still vulnerable to varicella, so a two-dose vaccination program should be implemented to prevent onward transmission of VZV.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Applying Spatio-temporal Scan Statistics and Spatial Autocorrelation Statistics to identify Covid-19 clusters in the world - A Vaccination Strategy?

With the whole world being affected by the pandemic, it is a matter of great importance that studies about spatial and spatio-temporal aspects of the COVID-19 (Sars-Cov-2) pandemic should be conducted, therefore the main goal of this paper is to present the Global Moran's I and the Local Moran's I used to evaluate spatial association in the number of deaths and infections by COVID-19, and a spatio-temporal Poisson scan statistic used to identify emerging or “alive” clusters of infections by Sars-Cov-2 in space and time. As of January 2021 vaccination against COVID-19 already started, since the use of spatial clustering methods to identify non-vaccinated populations is not new among studies on vaccination coverage strategies, this paper also aims to discuss the implementation of spatial and spatio-temporal clustering methods in early vaccination.

A practical approach to SARS-CoV-2 testing in a pre and post-vaccination era

As countries globally are in the process of planning, introducing or implementing mass vaccination strategies while continuing to deal with the ongoing SARS-CoV-2 pandemic, an evolution in testing strategies may be required to minimize spread in mixed vaccinated and non-vaccinated populations. This mini-review explores the key public health questions associated with the widely varying efficacy of commercially available vaccines and their persistence of protection in the context of a growing number of variant virus strains. A new strategy for SARS-CoV-2 testing that accommodates the current and evolving pandemic paradigm is proposed.

Therapeutic targeting of measles virus polymerase with ERDRP-0519 suppresses all RNA synthesis activity.

Morbilliviruses, such as measles virus (MeV) and canine distemper virus (CDV), are highly infectious members of the paramyxovirus family. MeV is responsible for major morbidity and mortality in non-vaccinated populations. ERDRP-0519, a pan-morbillivirus small molecule inhibitor for the treatment of measles, targets the morbillivirus RNA-dependent RNA-polymerase (RdRP) complex and displayed unparalleled oral efficacy against lethal infection of ferrets with CDV, an established surrogate model for human measles. Resistance profiling identified the L subunit of the RdRP, which harbors all enzymatic activity of the polymerase complex, as the molecular target of inhibition. Here, we examined binding characteristics, physical docking site, and the molecular mechanism of action of ERDRP-0519 through label-free biolayer interferometry, photoaffinity cross-linking, and in vitro RdRP assays using purified MeV RdRP complexes and synthetic templates. Results demonstrate that unlike all other mononegavirus small molecule inhibitors identified to date, ERDRP-0519 inhibits all phosphodiester bond formation in both de novo initiation of RNA synthesis at the promoter and RNA elongation by a committed polymerase complex. Photocrosslinking and resistance profiling-informed ligand docking revealed that this unprecedented mechanism of action of ERDRP-0519 is due to simultaneous engagement of the L protein polyribonucleotidyl transferase (PRNTase)-like domain and the flexible intrusion loop by the compound, pharmacologically locking the polymerase in pre-initiation conformation. This study informs selection of ERDRP-0519 as clinical candidate for measles therapy and identifies a previously unrecognized druggable site in mononegavirus L polymerase proteins that can silence all synthesis of viral RNA.

“Stick without a Carrot”: An Anthropological Analysis of the Daily Press on Mandatory MMR Immunization in Serbia

The vaccine is considered in academic, foremost medical, but also in political and public discourse as one of the greatest human achievements. Immunization has saved and is saving millions of lives around the world. However, from a historical perspective, immunization was always followed by more or less public resistance due to its alleged negative side-effects, such as outbursts of severe illnesses. A mandatory childhood vaccine against measles, mumps, and rubella (MMR) is part of the current controversy over the harmfulness of vaccines in Serbia. In view of the fact that the media is an important source for transmitting health messages and understanding health issues, the subject of this paper is the media presentation of MMR immunization in Serbia. How was the state health care narrative on MMR immunization presented in the Serbian daily press during the last two measles outbreaks in 2014-2015 and 2017-2018? By using the theoretical “text-context-hypertext” approcah to media content by Ljiljana Gavrilović, Serbian broadsheets and daily papers, such as Blic, Kurir, Politika, Večernje Novosti, from the period 2014-2020, are analyzed. The preliminary results show that the news that concurs with the 2014-15 measles epidemic differs greatly from the news during the 2017-18 epidemic. During the first period, the papers carried medical experts’ advice on the benefits and importance of the MMR vaccine, criticizing (irrational and emotional) parents (mostly mothers) who do not vaccinate their children, in parallel with parental lay evidence on its harmfulness. From approximately 2017 anti-vaccination attitudes disappeared from the newspapers, even from the yellow press. This is concomitant with the new Law on the Protection of the Population against Communicable Diseases (2016), which penalizes anti-vaccination lobbying. In other words, instead of gaining public trust in the health sector and the state by presenting facts, offering dialogue with opponents and systematic education, the state leaders discredited and excluded opposing opinions as “uncivilized”, “irrational” and part of “anti-vaccination lobbying”. Studies explained that citizens of post-socialist countries trust more individuals (friends and family) and distrust the state authorities (as enemies). By introducing compulsory penalties for non-vaccination, the state only deepened this historical and cultural distrust between the state and its citizen. To conclude, insults to parents of non-immunized children, threats of penalties and actual penalties, and the exaggeration of the outcomes of the 2014-15 measles epidemic did not lead to mass immunization. On the contrary, all this acted only counterproductively, as the latest epidemic broke out precisely among non-vaccinated and semi-vaccinated populations. Therefore, it is suggested in the paper that this vaccine should be optional, parallel with the introduction of organized promotion of MMR vaccination, its benefits and side-effects, detailed information on vaccine content, greater freedom of media content on the MMR vaccine, and open public dialogue of parents with medical experts.

Potential of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) to transmit yellow fever virus in urban areas in Central Africa

ABSTRACT Yellow Fever (YF) remains a major public health issue in Sub-Saharan Africa and South America, despite the availability of an effective vaccine. In Africa, most YF outbreaks are reported in West Africa. However, urban outbreaks occurred in 2016 in both Angola and the Democratic Republic of Congo (DRC), and imported cases were reported in Chinese workers coming back from Africa. In Central Africa, Cameroon and the Republic of Congo host a high proportion of non-vaccinated populations increasing the risk of urban outbreaks. The main vector is Aedes aegypti and possibly, Aedes albopictus, both being anthropophilic and domestic mosquitoes. Here, we provide evidence that both Ae. aegypti and Ae. albopictus in Cameroon and the Republic of Congo are able to transmit Yellow fever virus (YFV) with higher rates of infection, dissemination, and transmission for Ae. aegypti. We conclude that the potential of both Aedes species to transmit YFV could increase the risk of urban YF transmission and urge public health authorities to intensify their efforts to control domestic vectors, and extend vaccine coverage to prevent major YFV outbreak.

Research progression of prophylactic HPV vaccine application

Prophylactic HPV vaccine was a milestone in the prevention and control of HPV-related diseases, especially cervical cancer. The first HPV vaccine has been marketed in the world for more than 10 years. The follow-up study of HPV vaccine clinical trials further confirms the effectiveness and safety. Since HPV vaccine had been introduced into more and more national immunization programs, the population-level effectiveness of HPV vaccine was increasingly proved: Reduced the incidence of HPV infection, genital warts and high-grade precancerous lesions, and improved the herd immunity effect among non-vaccinated populations. However, improvement of the coverage of HPV vaccine, especially in low-and-middle income countries, is the major challenge in putting the HPV vaccine into practice.

Mumps in the Vaccination Age: Global Epidemiology and the Situation in Germany.

Vaccination against mumps virus (MuV) (mostly measles-mumps-rubella) is routinely performed in more than 120 countries and has resulted in a distinct decrease of mumps incidence. However, alteration of mumps epidemiology has been observed in several countries after implementation of the vaccine but is sparsely documented. Moreover, outbreaks have occurred after starting vaccination, even in highly vaccinated populations. In the former German Democratic Republic (DDR) mumps was a notifiable disease but vaccination against mumps was not implemented. In the five eastern German states forming the DDR until 1990, mumps was not notifiable until 2001. Except for the lack of reporting between 1990–2000, data from Eastern Germany allow analysis of mumps epidemiology after initiating the vaccination campaign. For the period from 2001 to 2016 the data show that the incidence of mumps dropped notably after initiating vaccines, and was accompanied by an increase of the median age of patients with mumps. In Eastern Germany, no outbreaks were noted, while several outbreaks occurred in Western Germany, possibly due to a lower vaccination rate. Further literature analysis revealed that outbreaks were facilitated by waning immunity and crowding. Nevertheless, although vaccination prevented infection, the course of illness, once infected, was sometimes more complicated. In comparison to non-vaccinated populations, high rates of complicated courses occurred and were marked by orchitis, due to higher age of mumps patients. Therefore, refusing vaccination against mumps increases the risk of severe courses when living in a vaccinated population.

Highly targeted cholera vaccination campaigns in urban setting are feasible: The experience in Kalemie, Democratic Republic of Congo.

IntroductionOral cholera vaccines are primarily recommended by the World Health Organization for cholera control in endemic countries. However, the number of cholera vaccines currently produced is very limited and examples of OCV use in endemic countries, and especially in urban settings, are scarce. A vaccination campaign was organized by Médecins Sans Frontières and the Ministry of Health in a highly endemic area in the Democratic Republic of Congo. This study aims to describe the vaccine coverage achieved with this highly targeted vaccination campaign and the acceptability among the vaccinated communities.Methods and findingsWe performed a cross-sectional survey using random spatial sampling. The study population included individuals one year old and above, eligible for vaccination, and residing in the areas targeted for vaccination in the city of Kalemie. Data sources were household interviews with verification by vaccination card. In total 2,488 people were included in the survey. Overall, 81.9% (95%CI: 77.9–85.3) of the target population received at least one dose of vaccine. The vaccine coverage with two doses was 67.2% (95%CI: 61.9–72.0) among the target population. The vaccine coverage was higher during the first round (74.0, 95%CI: 69.3–78.3) than during the second round of vaccination (69.1%, 95%CI: 63.9–74.0). Vaccination coverage was lower in male adults. The main reason for non-vaccination was to be absent during the campaign. No severe adverse events were notified during the interviews.ConclusionsCholera vaccination campaigns using highly targeted strategies are feasible in urban settings. High vaccination coverage can be obtained using door to door vaccination. However, alternative strategies should be considered to reach non-vaccinated populations like male adults and also in order to improve the efficiency of the interventions.

Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study.

Since their commercialization, vaccines against Porcine circovirus type 2 (PCV2) have been the cornerstone control strategy. Nevertheless, the periodic emergence of new genotype waves and the recent reports of vaccine failure outbreaks have raised the question if widespread vaccination strategies could have driven viral evolution and affected different genotype fitness. To investigate this issue an in-deep analysis, based on a bioinformatics and biostatistics approach, has been implemented. ORF2 sequences from vaccinated and non-vaccinated populations (i.e. domestic pigs before and after vaccine introduction and wild boars) were considered. The action of selective forces on PCV2 strains has been analyzed and compared among groups. Remarkable differences were found in the selective forces acting on viral populations circulating in different “immune environments”. Particularly for PCV2a, a directional selection promoting a change in the viral capsid away from the vaccine specific antigenic determinants has been detected after vaccine introduction. Involved amino acids were previously reported to be part of viral epitopes whose variability is responsible of immune escape. Our findings support a change in PCV2 evolutionary pattern after widespread vaccination introduction and stress once more the compulsoriness of a continuous monitoring of PCV2 epidemiology to promptly act in response to the emergence of possible vaccine-escaping mutants.

VECTOR ASPECTS IN RISK AREAS FOR SYLVATIC YELLOW FEVER IN THE STATE OF MATO GROSSO DO SUL, BRAZIL

As epidemias e epizootias de febre amarela ocorridas em 2008 no Brasil, Paraguai e Argentina marcaram um expressivo avanço da doença para o sul do continente, afetando populações humanas não vacinadas. O estado de Mato Grosso do Sul encontra-se na transição entre a região endêmica tropical e a epidêmica subtropical e, apesar de ser considerado área de recomendação para vacinação desde a década de 1980, ainda registra casos humanos e epizootias. O objetivo deste trabalho foi apresentar os resultados de levantamentos entomológicos em locais de casos humanos e epizootias notificados como suspeitos em 2008, descrevendo geograficamente essas áreas. Foram investigadas 13 localidades em nove municípios, tendo sido obtidas 305 fêmeas dos gêneros Haemagogus e Sabethes, além de cinco espécimes de Aedes albopictus. O gênero Haemagogus foi mais abundante, mas Sabethes apresentou o dobro de espécies (3 x 6) e maior distribuição entre os pontos de coleta. A espécie mais abundante foi Hg. janthinomys, porém com 102 indivíduos em um único local. As demais espécies encontradas foram: Hg. leucocelaenus, Hg.spegazzinii, Sa. albiprivus, Sa. belisarioi, Sa. chloropterus, Sa. glaucodaemun, Sa. intermedius e Sa. soperi. Não foi possível identificar tendências de preferência das espécies em relação aos atributos ambientais e geográficos descritos para os pontos de coleta. Dos nove casos humanos, oito corresponderam a pessoas não residentes no estado, sendo sete turistas. O estado de Mato Grosso do Sul reúne grande diversidade de atrativos turísticos relacionados com ambientes rurais e silvestres, onde o homem pode entrar em contato com os vetores da febre amarela encontrados neste trabalho. Nesse sentido, o monitoramento da cobertura vacinal e do fluxo de pessoas não vacinadas é fundamental para o controle da doença.

Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden

The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010.Over 90% of all invasive isolates during 2005–2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD).The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased.Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations.

Identification and characterization of a highly pathogenic H5N1 avian influenza A virus during an outbreak in vaccinated chickens in Egypt

Highly pathogenic avian influenza A (HPAI) H5N1 viruses continue to be a major veterinary and public health problem in Egypt. Continued surveillance of these viruses is necessary to devise strategies to control the spread of the virus and to monitor its evolutionary patterns. This is a report of the identification of a variant strain of HPAI H5N1 virus during an outbreak in 2010 in vaccinated chicken flocks in a poultry farm in Assiut, Egypt. Vaccination of chickens with an oil-emulsified inactivated A/chicken/Mexico/232/94 (H5N2) vaccine induced high levels of hemagglutination inhibition (HI) antibody titers reaching up to 9 log2. However, all flocks irrespective of the number of vaccine doses and the resultant HI titer levels came down with severe influenza infections. The qRT-PCR and rapid antigen test confirmed the influenza virus to be from H5N1 subtype. Sequencing of the hemagglutinin (HA) gene fragment from ten independent samples demonstrated that a single H5N1 strain was involved. This strain belonged to clade 2.2.1 and had several mutations in the receptor-binding site of the HA protein, thereby producing a variant strain of HPAI H5N1 virus which was antigenically different from the parent clade 2.2.1 virus circulating in Egypt at that time. In order to define the variability in HPAI H5N1 viruses over time in Egypt, we sequenced another H5N1 virus that was causing infections in chickens in 2014. Phylogenetic analysis revealed that both viruses had further distanced from the parent virus circulating during 2010. This study highlights that the antigenic mutations in HPAI H5N1 viruses represent a definitive challenge for the development of an effective vaccine for poultry. Overall, the results emphasize the need for continued surveillance of H5N1 outbreaks and extensive characterization of virus isolates from vaccinated and non-vaccinated poultry populations to better understand genetic changes and their implications.

Broad spectrum immunity against influenza viruses elicited by intranasal vaccination with a new recombinant subunit vaccine (VAC2P.924)

Abstract Frequent mutation of influenza viruses keep vaccinated and non-vaccinated populations vulnerable to new infections, causing serious burdens to public health and the economy. Vaccination with universal influenza vaccines would be the best way to effectively protect people from infection caused by mismatched or unforeseen influenza viruses. Presently, there is no FDA approved universal influenza vaccine. In this study, we expressed and purified a fusion recombinant protein CTB-3×M2e-HA2 which comprises of influenza matrix 2 protein ectodomain peptides, a centralized influenza hemagglutinin stem region, and cholera toxin subunit B. Intranasal vaccination of BALB/c mice with this novel artificial antigen resulted in potent humoral immune responses, including induction of antigen specific IgA and IgG, and broad protection against infection by multiple influenza viruses including mouse adapted H1N1 PR8, 2009 pandemic H1N1, and H3N2 influenza A viruses. Furthermore, our results demonstrated that when used as a mucosal antigen, cholera toxin subunit B improved antigen-stimulated T cell and memory B cell responses. Therefore, the candidate new nasal influenza vaccine has potential to be used in the event of a pandemic flu crisis, and provide relief to the public health burden.