After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases.

/pdf/the-evolution-of-poxvirus-vaccines-5faxd4wb1l.pdf

The Evolution of Poxvirus Vaccines

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(14)00002-X.pdf

Avian influenza vaccines against H5N1 ‘bird flu’

Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.

/pdf/viral-vector-based-influenza-vaccines-xjfykwvehq.pdf

Viral vector-based influenza vaccines.

Influenza is a vaccine preventable disease and vaccination remains the most effective method of controlling the morbidity and mortality of seasonal influenza, especially with respect to risk groups. To date, three types of influenza vaccines have been licensed: inactivated, live-attenuated, and recombinant haemagglutinin vaccines. Effectiveness studies allow an assessment of the positive effects of influenza vaccines in the field. The effectiveness of current influenza is suboptimal, being estimated as 40% to 60% when the vaccines strains are antigenically well-matched with the circulating viruses. This review focuses on influenza viruses and vaccines and the role of vaccine effectiveness studies for evaluating the benefits of influenza vaccines. Overall, influenza vaccines are effective against morbidity and mortality in all age and risk groups, especially in young children and older adults. However, the effectiveness is dependent on several factors such as the age of vaccinees, the match between the strain included in the vaccine composition and the circulating virus, egg-adaptations occurring during the production process, and the subject’s history of previous vaccination.

/pdf/influenza-viruses-and-vaccines-the-role-of-vaccine-3kil8ez1.pdf

Influenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines

Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines.

The immune response of a recombinant fowlpox virus coexpressing the HA gene of the H5N1 highly pathogenic avian influenza virus and chicken interleukin 6 gene in ducks

The continued emergence of human illness caused by avian influenza viruses (AIVs) demonstrates the threat of strains such as H5N1, H7N9, H10N8 and now H10N3. The genetic and biological properties of H10N3 viruses are not fully understood. In this study, three H10N3 strains isolated from live poultry markets (LPMs) were systematically studied. Genome sequencing showed that the poultry-origin viruses are highly homologous to the human H10N3 isolate. The three avian strains were A/chicken/Jiangsu/0146/2021(abbreviated as JS146, H10N3), A/chicken/Jiangsu/0169/2021 (JS169, H10N3) and A/chicken/Jiangsu/0189/2021(JS189, H10N3). Animal studies indicated that all three viruses are highly pathogenic to mice, and that all could replicate efficiently in mouse nasal turbinate and lungs despite maintaining their avian receptor binding affinity. We also found that these viruses replicated efficiently in A549 cells and chicken embryos. The strain JS146 had sensitivity to the neuraminidase-targeting drugs oseltamivir and zanamivir, whereas JS169 and JS189 were more resistant; genetic comparison implied that a substitution at NA position 368 conferred drug resistance. Importantly, several key molecular markers associated with mammalian adaptation had been detected in both avian and human-isolated H10N3 influenza viruses in the HA (G228S), PB2 (I292V and A588V), PB1 (M317V and I368V) and PA (A343S, K356R and S409N) protein. The above work contributes new insight into the biology of this potentially zoonotic subtype and provides evidence supporting the continued epidemiological monitoring of human infections caused by AIV subtype H10N3. This article is protected by copyright. All rights reserved.

Genetic and biological properties of H10N3 avian influenza viruses: a potential pandemic candidate?

Abstract The H9N2 subtype avian influenza virus (AIV) inactivated vaccine has been used extensively in poultry farms, but it often fails to stimulate a sufficiently high immune response in poultry in the field, although it works well in laboratory experiments; hence, the virus still causes economic damage every year and poses a potential threat to public health. Based on surveillance data collected in the field, we found that broilers with high levels of maternal-derived antibodies (MDAs) against H9N2 virus did not produce high levels of antibodies after vaccination with a commercial H9N2 inactivated vaccine. In contrast, specific pathogen-free (SPF) chickens without MDAs responded efficiently to that vaccination. When MDAs were mimicked by administering passively transferred antibodies (PTAs) into SPF chickens in the laboratory, similar results were observed: H9N2-specific PTAs inhibited humoral immunity against the H9N2 inactivated vaccine, suggesting that H9N2-specific MDAs might hinder the generation of antibodies when H9N2 inactivated vaccine was used. After challenge with homologous H9N2 virus, the virus was detected in oropharyngeal swabs of the vaccinated and unvaccinated chickens with PTAs but not in the vaccinated chickens without PTAs, indicating that H9N2-specific MDAs were indeed one of the reasons for H9N2 inactivated vaccine failure in the field. When different titers of PTAs were used to mimic MDAs in SPF chickens, high (HI = 12 log 2 ) and medium (HI = log 9 log 2 ) titers of PTAs reduced the generation of H9N2-specific antibodies after the first vaccination, but a booster dose would induce a high and faster humoral immune response even of PTA interference. This study strongly suggested that high or medium titers of MDAs might explain H9N2 inactivated vaccine failure in the field. 

/pdf/maternal-derived-antibodies-hinder-the-antibody-response-to-26j6aula.pdf

Maternal-derived antibodies hinder the antibody response to H9N2 AIV inactivated vaccine in the field

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The immune response of a recombinant fowlpox virus coexpressing the HA gene of the H5N1 highly pathogenic avian influenza virus and chicken interleukin 6 gene in ducks

Genetic and biological properties of H10N3 avian influenza viruses: a potential pandemic candidate?

Maternal-derived antibodies hinder the antibody response to H9N2 AIV inactivated vaccine in the field