Influenza Vaccine Effectiveness and Immune Response

Seasonal and pandemic influenza viruses pose a persistent global health challenge, driving substantial morbidity and mortality each year. Vaccination remains the primary public health tool for prevention, yet effectiveness varies widely by age group, virus subtype and vaccine formulation. Immune protection primarily relies on antibodies directed against surface glycoproteins—haemagglutinin and neuraminidase—together with T-cell responses that limit disease severity. Vaccine performance is influenced by antigenic match between vaccine strains and circulating viruses, production methods (for example egg-adaptation), host factors such as age and comorbidities, and adjuvant use. In addition, emerging insights into innate and lipid-mediated pathways highlight mechanisms underpinning severe disease. Recent efforts focus on broadened antibody targets, improved correlates of protection beyond haemagglutination inhibition and novel platforms designed to elicit durable cross-subtype immunity. Advances in global surveillance and standardised efficacy assessments have refined recommendations for high-dose, adjuvanted or recombinant vaccines in vulnerable populations. Continued integration of immunological biomarkers, structural biology and clinical outcomes promises to enhance vaccine design and deployment strategies, with the ultimate goal of universal influenza prevention.

Research from Nature Portfolio

Recent studies have described a monoclonal antibody that targets the highly conserved active site of neuraminidase rather than the variable haemagglutinin head. This antibody exhibits broad neutralisation across all group 1 and group 2 influenza A and B viruses, including drifted H3N2 and ancestral lineages. Structural analysis revealed that the complementarity-determining region of the antibody mimics sialic acid binding, potently inhibiting enzymatic function. In murine models, prophylactic administration conferred robust protection against lethal influenza challenge, supporting development of neuraminidase-directed immunogens as supplements or alternatives to current vaccines and highlighting synergistic activity when combined with stem-directed haemagglutinin antibodies.

Influenza Vaccine Effectiveness and Immune Response publication trend

The graph below shows the total number of articles in influenza vaccine effectiveness and immune response across all publications each year (not limited to Nature Index journals).

Technical terms

Haemagglutinin (HA): A viral surface glycoprotein that mediates attachment of influenza virus to host cells and a primary target of neutralising antibodies.

Neuraminidase (NA): A viral surface enzyme essential for release of progeny virions from infected cells and a secondary vaccine target.

Haemagglutination inhibition (HAI) titre: The serum antibody concentration required to prevent agglutination of red blood cells by virus, traditionally used as a correlate of protection.

Neuraminidase inhibition (NAI) titre: The serum antibody level necessary to inhibit neuraminidase enzymatic activity, increasingly recognised as a critical correlate of clinical protection.

Adjuvanted vaccine: A formulation that includes an immunostimulatory substance to enhance the magnitude, breadth or durability of the immune response.

Egg-adaptation: Mutations arising when vaccine viruses are propagated in eggs, which can alter antigenicity and reduce effectiveness against circulating strains.

References

1. A pan-influenza antibody inhibiting neuraminidase via receptor mimicry. Nature (2023).
2. High expression of oleoyl-ACP hydrolase underpins life-threatening respiratory viral diseases. Cell (2024).
3. Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model. mBio (2016).
4. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024–25 Influenza Season. MMWR Recommendations and Reports (2024).