Lessons from the Mechanism of Protection by Vaccines vis-à-vis Low Effectiveness of Influenza Vaccines – What can be done?

Except for safe water, vaccines have been the most effective public health intervention in reducing mortality and morbidity due to many infectious diseases. One of the deadliest diseases in the history of mankind, smallpox and its causative agent, the smallpox virus, has been eradicated from the planet by universal vaccination with the smallpox vaccine. Polio has been eliminated from the Western Hemisphere through effective vaccination campaigns. While measles was eliminated, imported cases still pose a threat to unvaccinated individuals and those who are immunocompromised.

Vaccines have also controlled many other diseases with high morbidity and mortality, including tetanus, diphtheria, pertussis, typhoid, mumps, rubella, chicken pox, shingles, yellow fever, diseases caused by hepatitis B, hepatitis A, human papillomavirus, Pneumococci, Meningococci, and Haemophilus influenzae type b, etc. Vaccines benefit people of all ages, protecting the health of the elderly and vulnerable from infectious diseases and preventing infection-related cancers. They also reduce the risk of transmitting disease to others in the community, providing herd immunity.

Most vaccines confer protection by inducing antibodies to virulence factors of the pathogen, which neutralize the toxins secreted by bacteria and kill the viruses or bacteria. Over time, antibody levels decline, but protection against most diseases is maintained through the rapid deployment of B-memory cells in response to antigens from invading pathogens. Maintaining high antibody levels is crucial for toxin-mediated diseases like tetanus and diphtheria. Other protective mechanisms include cytotoxic CD8+ T lymphocytes, CD4+ T-helper (Th) lymphocytes, & mucosal immunity. After completing the primary vaccination series, booster doses are not required for most vaccines. However, influenza vaccination is recommended annually due to the evolving nature of influenza viruses through antigenic drift and a decrease in antibody levels. Despite annual vaccination, the effectiveness of influenza vaccines is variable and often low. Factors for the low effectiveness of influenza vaccines include the antigenic drift of influenza viruses and how annual influenza vaccines are designed based on the projection of circulating strains for the upcoming influenza season from global surveillance of circulating influenza strains from the prior influenza season in the opposite hemisphere. Other factors affecting the effectiveness of influenza vaccines include the manufacture of most vaccines in embryonated chicken eggs, causing a mismatch between egg-adapted haemagglutinin (HA) antigen and HA on circulating strains, annual or repeated vaccination, and original antigenic sin leading to not generating an immune response to new epitopes on HA of emerging strains through immune tolerance, hijack of the immune system to conserved epitopes, & immune refractoriness. The current yearly flu vaccine policy is ineffective. It harms the immune system through an increase in HA-specific regulatory T (Treg) cells, which can suppress the immune system's ability to fight off flu infections, both antibody production (humoral response) and cell-mediated immune response. The root cause for the failure of the current influenza vaccination policy and the ineffectiveness of influenza vaccines is the corporate greed of pharmaceutical companies and the inaction and indecisiveness of our public health institutions, including CDC, NIH, FDA, and WHO, despite overwhelming scientific data. Unfortunately, these agencies & corporate greed are taking COVID-19 vaccination in the same direction. The vaccination strategy and policy with influenza vaccines need significant changes along with other ways to control influenza infections, such as anti-viral drugs, passive immunization of high-risk patients with monoclonal antibodies, and preventive behavioral measures, such as mask-wearing, hand washing, and social distancing or contact avoidance. These preventive behavioral measures shall not protect against influenza only, but from other respiratory viral diseases, including COVID-19, respiratory syncitial virus infection, common cold and new emerging human metapneumovirus (hMPV) infections.

New influenza vaccines need to be developed from the influenza viruses isolated in cell cultures rather than eggs, and the annual vaccination policy should be stopped.