Innovations and Challenges in Influenza Vaccine Development and

Global Deployment

Yujin Hao

Shanxi Medical University, Taiyuan, Shanxi Province, China

Keywords: Influenza Vaccines, Vaccine Platforms, Global Deployment.

Abstract: Influenza remains a major global public health challenge, causing an estimated 290,000 to 650,000

respiratory-related deaths annually. Traditional egg-based vaccines are limited by slow production cycles and

reduced efficacy due to antigenic drift. In contrast, mRNA and recombinant protein vaccines have improved

production speed and immune response. mRNA vaccines offer up to 89.6% protection against H1N1, while

recombinant vaccines have enhanced efficacy in older adults by 30%. Despite these advances, challenges

such as high costs, cold-chain requirements, and low global vaccination coverage hinder effective control.

This review highlights recent vaccine design innovations and evaluates ongoing issues, including viral

evolution, immune durability, and access disparities.

1 INTRODUCTION

According to the statistics of the World Health

Organization, there are about 1 billion cases of

influenza worldwide every year. Among them, 3 to 5

million were severe cases and 290,000 to 650,000

died from respiratory infections (WHO, 2023). High-

risk population (such as children, the older and people

with low immune function) are more prone to

complications such as pneumonia, myocarditis and

multiple organ dysfunction. Historical seasonal

influenza epidemics and major influenza pandemic,

such as “Spanish flu” in 1918 and influenza A H1N1

in 2009, have not only increased the global healthcare

burden, but also posed serious challenges to social

and economic stability (Saunders-Hastings &

Krewski, 2016). Influenza vaccination is the most

effective way to prevent influenza, which can reduce

the risk of infection by 60% to 70% and the risk of

hospitalization by 40% to 60% (Andrew et al., 2017).

Therefore, large-scale vaccination is very important

to reduce the burden on the medical system.

Traditionally, inactivated vaccines and attenuated

live vaccines are always the main prevention and

control tools (Osterholm et al., 2012). In recent years,

new vaccine platforms based on mRNA technology

and recombinant protein vaccines have developed

rapidly (Pardi et al., 2018). By precisely targeting

viral surface proteins (such as hemagglutinin HA),

immunogenicity is significantly improved. Despite

the continuous progress of vaccines technology, the

development of influenza vaccine still faces many

challenges. Firstly, the influenza virus undergoes

rapid mutation. It allows the virus to escape immune

identification through antigen drift and antigen

changes. This means that the effectiveness of the flu

vaccine fluctuates every day. For example, in 2014 to

2015, the efficiency of vaccines in North America

was only 19%. Production constraints—including a

six‑month egg‑based manufacturing cycle and

potential culture‑induced antigenic changes—further

impede timely vaccine updates (Zost et al., 2017).

Additionally, global vaccination coverage remains

suboptimal (below 50% on average), driven in part by

vaccine hesitancy and “vaccine fatigue.”

Despite substantial advances in influenza vaccine

research and development, further interdisciplinary

collaboration and technological innovation are

essential to optimize vaccine efficacy and

accessibility. This review systematically examines

emerging influenza vaccine strategies—including

universal vaccine design, adjuvant optimization, and

advanced delivery systems—and evaluates critical

challenges such as limited immune durability,

inequitable global efficacy, and the need for mucosal

immunity. By providing a comprehensive analysis of

recent R&D progress, identifying persistent

obstacles, and outlining future directions, this review

seeks to furnish a scientific foundation and actionable

guidance for enhancing influenza prevention and

control.

426

Hao, Y.

Innovations and Challenges in Inﬂuenza Vaccine Development and Global Deployment.

DOI: 10.5220/0014494500004933

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science (BEFS 2025), pages 426-429

ISBN: 978-989-758-789-4

2 THE GLOBAL IMPACT OF

INFLUENZA VIRUS AND

HIGH-RISK GROUPS

Influenza virus is one of the fastest and most frequent

respiratory viruses in the world. It puts great pressure

on the global public health system every year.

According to the statistics of the World Health

Organization, 290,000 to 650,000 people suffer from

respiratory diseases every year (Iuliano et al., 2018).

In countries with poor health conditions, the mortality

rate is two to three times that of developed countries

(Global Burden of Disease Collaborative Network,

2021). The risk of infection varies significantly

among different groups of people: children under the

age of 5 are three times more likely to suffer from

serious diseases than normal children because of their

immature immune systems, while the elderly over 65

years old account for 80% of flu deaths. This is

because their immune system is weak and often

accompanied by chronic disease (such as

hypertension, diabetes, etc.), making them more

prone to complications after infection with influenza

(Paget et al., 2022). According to the statistics of

Chinese hospitals, among the elderly over 60 years

old, 42.3% of flu patients are serious cases, and the

mortality rate of heart disease and diabetes patients is

as high as 12.7% (Li et al., 2021). In addition, the

immunity of pregnant women is relatively low, so

they are more likely to be infected with the flu and

enter intensive care than ordinary women. The health

status of these high-risk groups makes influenza more

harmful to them, highlighting the urgency of

influenza prevention and control (Rasmussen et al.,

2022). Other high‑risk groups include individuals

with immunodeficiency (e.g. HIV infection, organ

transplant recipients), residents of long‑term care

facilities, and persons with obesity or chronic

respiratory conditions. These populations not only

suffer higher rates of hospitalization and death but

also contribute disproportionately to healthcare

utilization and economic costs. Collectively, these

data underscore the critical need for targeted

prevention strategies and enhanced vaccine coverage

to mitigate the substantial global impact of influenza.

3 THE MUTATION MECHANISM

OF INFLUENZA VIRUS

The high variability of the influenza virus is the main

reason for its long-term challenge to the effectiveness

of vaccine prevention and control. The mutation

mechanism of influenza virus includes two forms:

antigen drift and antigen transformation. Antigen drift

refers to the gradual changes of surface antigens (such

as hemagglutinin, neuraminidase, etc.) due to

replication errors in the replication process of

influenza viruses, which makes the virus escape the

recognition of the host's immune system (Wu et al.,

2020). This change is one of the ways the influenza

virus adapts to the environment and escapes immune

surveillance. For example, the vaccine used in North

America in 2014 could not prevent 19% of diseases,

because there was a mutation in the surface antigen

part between the vaccine used that year and the virus

that was actually prevalent, which greatly reduced the

effectiveness of the vaccine (Neher & Bedford,

2021). Another important form of mutation is antigen

transformation, which usually occurs in the process

of viral gene exchange or recombination between

different animals (such as pigs, birds, etc.) and

humans. For example, the 2009 H1N1 pandemic

strain emerged through genetic reassortment of avian,

swine, and human influenza viruses, resulting in

widespread global transmission (Petrova & Russell,

2018). Such major antigenic changes can render prior

immune memory ineffective, necessitating rapid

vaccine reformulation (Arevalo et al., 2022).

Consequently, continuous viral evolution remains a

critical obstacle to the timely development and

updating of effective influenza vaccines.

4 TYPES AND CHALLENGES OF

INFLUENZA VACCINES

At present, there are two main types of vaccines:

inactivated vaccines and live attenuated vaccines.

Inactivated vaccines can bind with viruses and retain

the protective factor structure on the surface of the

virus, while the treatment of live vaccines can prevent

the virus from multiplying in the nasal cavity or

spreading in the hair (Grohskopf et al., 2020). The

advantage of inactivated vaccines is that they are safe

and suitable for most people, including the elderly

and patients with low immune function. However, the

disadvantage of inactivated vaccines is that they have

poor immune protection against some viruses, mainly

because they stimulate the production of antigens in

the blood. For example, the protection rate against the

H3N2 virus is only 33% to 44%, and it can only

stimulate the antibody reaction in the blood, making

it difficult to effectively activate the local immune

response (Osterholm et al., 2022). Live attenuated

vaccines allow the virus to multiply in the nasal cavity

Innovations and Challenges in Inﬂuenza Vaccine Development and Global Deployment

427

without causing serious systemic infections by

attenuating its pathogenicity. This vaccine activates

the nasal and cellular immune systems, providing

children with a higher rate of protection, 72% to 83%.

However, there are certain restrictions on the use of

live attenuated vaccines. People with weak immune

systems or health problems (such as immunodeficient

people) are not suitable for vaccination, because it

may cause serious side effects, such as nasal

congestion and severe fever (Blshe et al., 2021;

Centers for Disease Control and Prevention, 2023).

Among the elderly, the content of antibodies

decreased by 10% within 6 months after vaccination,

resulting in a great reduction in the effectiveness of

the vaccine (Black et al., 2011). In addition, the

traditional influenza vaccine production relies on

chicken embryo culture, which is not only time-

consuming but also prone to virus mutation during

culture. For example, when H3N2 virus is cultured in

chicken embryos, the mutation in amino acid No. 160

will affect the effect of the vaccine (Zost et al., 2020).

In 2017, because of this mutation, vaccines in the

northern hemisphere were 20 per cent less effective

compared to cell-cultured vaccines. World vaccine

production is concentrated in a few countries, while

vaccination rates in developing countries are below

30% (WHO, 2022), further exacerbating the global

imbalance in vaccination.

5 NEW VACCINE PLATFORM

AND DEVELOPMENT

With the advancement of science and technology, the

emergence of novel vaccine platforms has provided

new solutions for the development of influenza

vaccines. mRNA vaccines have been one of the most

interesting research directions in recent years. The

mRNA vaccine uses lipid nanoparticles to wrap the

mRNA gene of the virus. After injecting into the

human body, mRNA instructs cells to synthesize the

surface antigen of the virus, thus stimulating the

immune system to produce antibodies and cellular

immune responses. Clinical experiments show that

the protection rate of mRNA vaccine against H1N1

virus has reached 89.6%, and the production cycle has

been greatly shortened to two months (Zhang et al.,

2021). Nevertheless, there is still a risk of allergy in

vaccines. There are about 2.8 cases of allergy per

100,000 injections, and they need to be stored at

extremely low temperatures (-70°C) to maintain their

stability, which poses challenges to large-scale

production and distribution (Pardi et al., 2022).

Fortunately, with the improvement of the formula, the

existing mRNA vaccine can be stored in a refrigerator

at 4°C for a month, which greatly simplifies the

logistics and distribution (Gebre et al., 2022).

Recombinant prokaryotic vaccines (such as Flublok)

use insect cells to produce viral nuclei, thus avoiding

the mutation problems associated with worm culture.

These vaccines are 30 per cent more effective than the

regular vaccine in people over 65 years of age,

however they are also relatively expensive, costing

$28.50 per dose, three times as much as the regular

vaccine (Dunkle et al., 2022). Despite the

technological breakthroughs of the new vaccine

platform, cost issues and the enhancement of large-

scale production capacity are still challenges that

need to be addressed.

6 CONCLUSION

This review shows that the current influenza vaccine

system is facing a critical period of technological

change. Due to the possibility of virus mutation, such

as the antigen mutation of H3N2 in 2017 and the

extension of production time, it is difficult for

traditional egg-based culture technology to cope with

rapidly developing viruses. Although novel vaccine

platforms offer substantial benefits—mRNA vaccines

can be manufactured within two months, and

recombinant protein vaccines improve protection in

older adults by approximately 30%—high production

costs, stringent cold‑chain requirements, and logistical

complexities continue to present significant

challenges. The most important conflict is the

competition between the rate of virus evolution and

vaccine effectiveness. Current predictive models are

outdated, shortening the duration of vaccine protection,

while vaccine coverage in developing countries is

below 30 per cent and the gap between prevention and

control is widening. Closing the gap between viral

mutation and vaccine responsiveness requires

integrated strategies: deploying artificial intelligence–

driven real‑time genomic surveillance and predictive

modeling to guide strain selection and support

universal vaccine design; advancing novel delivery

approaches, including intranasal formulations, to

strengthen mucosal immunity and prolong protection;

and building a coordinated, modular manufacturing

infrastructure that combines cell‑based production

with nanoparticle technologies to lower costs and

expand capacity. Through sustained international

collaboration and continued innovation, it is possible

to establish a more agile, effective, and universally

accessible influenza prevention framework.

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