The combined influenza vaccine COVID protects against current and emerging variants of the animal model

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The unprecedented development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over the past twelve months appears to be mitigating the COVID-19 epidemic in geographies where implementation has been successful. The deployment of more than a dozen vaccines, with many more ready, has brought hope that the pandemic may end and that life may soon return to normal.

Temporary reduction of influenza

Non-pharmaceutical interventions (NPIs), such as blockades, the use of masks, social distancing, and the closure of non-essential institutions, have led to a temporary reduction in cases and deaths in most regions where to apply. Along with the sharp drop in COVID-19 cases, seasonal flu has also shown a drastic decline during the pandemic.

However, as vaccine uptake becomes more robust globally, social and business interactions are likely to increase and the flu will return, according to the researchers. As antigenic drift occurs, new strains will emerge, including potentially new strains. This may lead to a new flu pandemic.

Seasonal flu takes about 400,000 lives each year, on average, but four major flu pandemics have already occurred over the past century. The Spanish H1N1 flu of 1918-1919 with 50 million deaths, the Asian flu 1957-1959 H2N2 with 1.5 million deaths, the H3N2 flu of 1968-1969 H3N2 with one million deaths and the H1N1pdm09 swine flu of 2009- 2010 with between 150,000 and 575,000 deaths worldwide.

Combined components of the vaccine

Now, in a new research published in the bioRxiv* prepress server, Novavax, Inc. scientists present a vaccine that includes recombinant influenza hemagglutinin (HA) antigen together with recombinant SARS-CoV-2 ear protein, with Matrix-M saponin adjuvant. Both have passed independent safety tests in phase 1 tests.

The quadrivalent nanoparticle influenza (qNIV) vaccine has repeatedly been shown to elicit widespread protective immunity against older and emerging strains, probably due to the highly conserved neutralizing epitopes of the HA stem domain and the rudimentary esterase domain. Both hemagglutination inhibition (HAI) and microneutralizing (MN) antibodies have been produced against older and newer A and B strains of H3N2 and H1N1 viruses.

Previous researchers employed a platform for the production of recombinant insect cells for the generation of nanoparticles carrying the full-length SARS-CoV-2 spike stabilized in the prefusion conformation. These proteins are shaped like trimers that form rosettes when associated with polysorbate 80 (PS 80) micelles.

Antibodies caused by this vaccine were protective against Wuhan-Hu-1 USA-WA1-like virus, as well as the UK (B.1.1.7) and South African (B.1.351) SARS-CoV- variants. 2. When tested in mice and in two monkey models, the vaccine prevented upper and lower respiratory tract infections after exposure to this virus.

The safety, tolerability, and immunogenicity of vaccines have been established in many trials, showing that it induces a Th1 -biased CD4 + T cell response.

Therefore, the two components of this vaccine have been tested individually to test their safety and efficacy.

Influenza virus neutralizing antibodies in hamsters immunized with combined vaccine qNIV / CoV2373. Groups of hamsters were immunized with the qNIV / CoV2373 combination or with the component vaccines, as shown in Figure 2A. Virus-neutralizing titers were determined 14 days after dose and 14 days after booster immunization (day 28 of the study). (A, B) A / Kansas / 14/2017. (C, D) A / Brisbane. / 02/2018. (E, F) B / Phuket / 3073/2013. (G, H) B / Maryland / 15/2016. Bars indicate geometric mean titer (GMT) and error bars indicate 95% confidence interval. The horizontal dashed line indicates the detection limit (LOD).

Combined vaccine resource

In the current study, it was shown that the combination of QNIV and ear vaccines retains its protective capabilities against influenza A and B, through HAI and neutralizing antibodies, while protecting against upper and lower respiratory infection with SARS-CoV-2. The researchers took advantage of this unique pandemic situation along with data from the qNIV vaccine trial to develop this new combination.

Although previous vaccines were almost always intended for use in children, the current vaccine offers a low-risk route for approval, as the HA influenza component has been shown to cause protective levels of influenza. immunity, as well as the recombinant spike protein component.

Protection against emerging variants

In addition, the combined vaccine offers protection against emerging variants of SARS-CoV-2, which is an essential requirement in the current situation. Viruses like this, with a ribonucleic acid (RNA) genome, are known to mutate rapidly and often, especially when faced with immune responses from host cells and organisms, and in the case of zoonoses such as SARS-CoV. -2, due to change as well.

The South African variant of SARS-CoV-2 has been shown to adapt to immune challenges through escape mutations that allowed recurrent outbreaks among a population group that is thought to have achieved population immunity. The use of spike protein based on nanoparticles allows to expose cryptic epitopes, taking advantage of the epitopes conserved between this variant and the prototype strain.

This could include causing antibodies that are not obtained by natural infection.

The flu vaccine also appeared to show little efficacy in the field, as evidenced by the occurrence of several seasonal outbreaks of severe influenza due primarily to strains A (H3N2). Apparently, this is due to differences in antigens when generated in egg-based vaccines, but also due to antigenic changes in viruses.

However, it has recently been shown that the recombinant nanoparticle flu vaccine (HAV) adjuvanted by Matrix-M induces immunity to highly conserved epitopes with great neutralizing capacity.

The use of full-surface HA glycoprotein allows the wild-type circulating viral sequence to be maintained while allowing cryptic epitopes to be exposed to the immune system and thus elicit widely neutralizing polyclonal antibodies.

Previous studies showed that this formulation improved the HAI immune response against A / H3N2 variants resulting from antigenic drift for several years, compared to the high-dose inactivated trivalent influenza vaccine (IIV3-HD).

What are the implications?

Suppression of influenza is not only likely to be transient, but co-infections with both influenza and SARS-CoV-2 will become more frequent. The flu will often be overlooked because of its similarity symptoms of COVID-19.

Admitting that the outcome of these coinfections is unknown, it is urgent to prepare for this eventuality using a combined vaccine like this. Not only does it avoid the need for separate vaccine logistics, but it protects against current and emerging strains of both viruses.

* Important news

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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