scholarly journals Is It Possible? A Different Approach to Creating a Universal Influenza Vaccine

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Virus Infection ◽  
Emerging Viruses ◽  
The Public ◽  
Influenza Virus Hemagglutinin ◽  
Health Community ◽  
Universal Influenza Vaccine ◽  
Virus Strains

ABSTRACT The best way to combat influenza virus infection is to prevent it. However, the continual evolution of circulating influenza virus strains and the constant threat of newly emerging viruses forces the public health community to annually update seasonal influenza vaccines while stockpiling potential pandemic virus vaccines. Thus, there is an urgent need to develop a “universal” influenza vaccine that affords protection against all strains. In their recent article, L. M. Schwartzman et al. (mBio 6:e01044-15, 2015, doi:10.1128/mBio.01044-15) demonstrated that intranasal immunization of mice with a cocktail of viral-like particles (VLPs) expressing distinct influenza virus hemagglutinin (HA) proteins can broadly protect against infection not only with the same viral strains but also with unrelated strains. These findings suggest a promising strategy for developing a broadly protective “universal” influenza vaccine.

scholarly journals A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses

2019 ◽  
Author(s):  
Jiong Wang ◽  
Alexander Wiltse ◽  
Martin S. Zand
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Antibody Response ◽  
Influenza Vaccine ◽  
Herd Immunity ◽  
Influenza Virus Infection ◽  
Minimal Amount ◽  
Human Antibody ◽  
Humoral Immune ◽  
Universal Influenza Vaccine

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

scholarly journals Development of a Pan-H1 Influenza Vaccine

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Nicole Darricarrère ◽  
Svetlana Pougatcheva ◽  
Xiaochu Duan ◽  
Rebecca S. Rudicell ◽  
Te-Hui Chou ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
The Past ◽  
Individual Strain ◽  
Humoral Responses ◽  
Virus Strains

ABSTRACT The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine. IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses.

scholarly journals Targeting Antigens for Universal Influenza Vaccine Development

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 973
Author(s):  
Quyen-Thi Nguyen ◽  
Young-Ki Choi
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Influenza Viruses ◽  
Target Antigen ◽  
Cell Responses ◽  
Universal Influenza Vaccine ◽  
Virus Strains

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.

scholarly journals A Complex Dance: Measuring the Multidimensional Worlds of Influenza Virus Evolution and Anti-Influenza Immune Responses

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 238 ◽  
Author(s):  
Jiong Wang ◽  
Alexander Wiltse ◽  
Martin S. Zand
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Antibody Response ◽  
Influenza Vaccine ◽  
Herd Immunity ◽  
Influenza Virus Infection ◽  
Minimal Amount ◽  
Human Antibody ◽  
Humoral Immune ◽  
Universal Influenza Vaccine

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A “universal” influenza vaccine that could induce broad cross-influenza subtype protection would help to address this issue. However, the human antibody response is intricate and often obscure, with factors such as antigenic seniority or original antigenic sin (OAS), and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

scholarly journals 997. Protection of Unvaccinated Individuals by Influenza Vaccine Coverage of Household Contacts

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S296-S297
Author(s):  
Ryan E Malosh ◽  
Richard Evans ◽  
Emily T Martin ◽  
Joshua G Petrie ◽  
Arnold S Monto
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Indirect Effects ◽  
Seasonal Influenza ◽  
Vaccine Coverage ◽  
Influenza Virus Infection ◽  
Seasonal Incidence ◽  
Household Contacts ◽  
Close Contacts

Abstract Background The evidence that influenza vaccination programs provide some protection to unvaccinated members of a community (i.e., indirect effects) is lacking. We sought to determine the indirect effects of influenza vaccine in prospective cohort study of households with children. Methods We used longitudinal data over six influenza seasons from the Household Influenza Vaccine Evaluation (HIVE) study. We categorized households each season based on the proportion of members who received a seasonal influenza vaccination: unvaccinated (0%), low coverage (1–50%), moderate coverage (50–99%), and fully vaccinated (100%). We used mixed-effect Poisson regression models adjusted for age group and sex with random effects to account for household clustering and repeated measures. We estimated the association between the proportion of vaccinated household members and the incidence of influenza virus infection in the entire cohort. We then estimated the indirect effects of influenza vaccination by comparing unvaccinated members of households with low levels of vaccination to unvaccinated members of households with higher levels of vaccination. Results During 7,286 person-seasons of follow-up, we detected 578 cases (8 per 100/season) of influenza virus infection. The seasonal incidence rate was highest in completely unvaccinated households (10 per 100/seasons) and lower at all other levels of vaccine coverage (Figure 1). Individuals in fully vaccinated households had a 29% lower seasonal incidence rate of influenza infection compare to those in unvaccinated households (IRR 0.72, 95% CI 0.56–0.93). The estimated indirect VE comparing unvaccinated individuals in completely unvaccinated households to those in households with moderate vaccine coverage was 40 % (95% CI −4 to 65). Conclusion We demonstrate that vaccination of close contacts can reduce incidence of influenza in unvaccinated members of a community. Despite insufficient evidence, guidance from public health authorities currently suggests that vaccination protects close contacts. Our findings quantifying the protective effects of seasonal influenza vaccination of household contacts in unvaccinated individuals can provide clearer evidence for global vaccine recommendations. Disclosures All authors: No reported disclosures.

scholarly journals Changes in RNA secondary structure affect NS1 protein expression during early stage influenza virus infection

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Irina Baranovskaya ◽  
Mariia Sergeeva ◽  
Artem Fadeev ◽  
Renata Kadirova ◽  
Anna Ivanova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Secondary Structure ◽  
Protein Expression ◽  
Rna Secondary Structure ◽  
Reverse Genetics ◽  
Early Stage ◽  
Influenza Virus Infection ◽  
Main Function ◽  
Ns1 Protein ◽  
Virus Strains

AbstractRNA secondary structures play a key role in splicing, gene expression, microRNA biogenesis, RNA editing, and other biological processes. The importance of RNA structures has been demonstrated in the life cycle of RNA-containing viruses, including the influenza virus. At least two regions of conserved secondary structure in NS segment (+) RNA are predicted to vary among influenza virus strains with respect to thermodynamic stability; both fall in the NS1 open reading frame. The NS1 protein is involved in multiple virus-host interaction processes, and its main function is to inhibit the cellular immune response to viral infection. Using a reverse genetics approach, four influenza virus strains were constructed featuring mutations that have different effects on RNA secondary structure. Growth curve experiments and ELISA data show that, at least in the first viral replication cycle, mutations G123A and A132G affecting RNA structure in the (82–148) NS RNA region influence NS1 protein expression.

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