Understanding Population Immunity and Vaccine Effectiveness in the Face of Emerging COVID-19 Variants

As COVID-19 cases decline, the focus shifts to understanding population immunity and the effectiveness of vaccines in preventing severe disease in the face of emerging variants according to research published in Human Vaccines & Immunotherapeutics. 

COVID-19 caused by SARS-CoV-2 has resulted in global morbidity and mortality since late 2019, with severe cases leading to acute respiratory distress syndrome and overwhelming hospital resources. Vaccines developed in response to the pandemic have shown efficacy against symptomatic infection, but emerging variants have raised concerns about waning immunity. Despite challenges posed by new variants, vaccines still offer substantial protection against severe disease, prompting further research and development to enhance immune responses and patient outcomes.

SARS-CoV-2 primarily infects respiratory mucosal surfaces in the upper pharynx, with many cases showing mild to moderate symptoms, progressing to severe COVID-19 in unvaccinated individuals one week after symptoms develop. Acute respiratory distress syndrome (ARDS), characterized by hypoxemia and respiratory failure, can lead to high mortality rates among those who require mechanical ventilation. The progression to ARDS in COVID-19 patients is likely due to a virus-induced injury to alveolar cells and a dysregulated immune response, leading to excessive inflammation and tissue damage. In severe cases, ARDS can result in diffuse alveolar damage and the formation of fibrin-rich hyaline membranes in the lungs, ultimately impacting patient survival. The use of vaccines, antiviral drugs, and treatments targeting inflammation have been shown to significantly reduce mortality rates among COVID-19 patients and control the severity of the disease.

A rise in breakthrough COVID-19 cases was reported due to waning neutralizing antibody (NAb) titers despite the initial vaccine efficacy in 2020. Several waves of SARS-CoV-2 variants that escape vaccine-elicited NAbs have emerged since the phase 3 clinical trials.

Inducing a robust memory immune response in the upper respiratory tract could prevent the acquisition of SARS-CoV-2 by targeting the nasopharynx and oral mucosa. Research suggests that intramuscular vaccines may not fully replicate the mucosal responses seen in natural infection, leading to potential weaknesses in protection against the virus. Studies in animals and pre-clinical trials have shown that mucosal administration of COVID-19 vaccines can generate strong mucosal immune responses that offer enhanced protection against infection and emerging variants.

Approximately 13 billion doses of COVID-19 vaccines have been administered globally since late 2020, with 70% of the population receiving at least one dose. Despite the emergence of highly transmissible variants leading to multiple waves of cases, vaccines continue to offer strong protection against severe COVID-19. While vaccine efficacy against mild infection may decrease, protection from severe disease remains high across different vaccine platforms due to robust B-cell and T-cell responses.

The adaptive immune response to SARS-CoV-2 infection involves humoral and cellular immunity, critical for resolving the infection. Antibodies and CD8+ T-cells play important roles in preventing viral entry and clearing infected cells. T-cell responses, especially to conserved viral epitopes, are crucial in controlling infection and preventing severe disease. Studies have shown that T-cells, rather than antibodies, can mediate disease resolution and protect against severe outcomes, particularly in cases of breakthrough infection or in individuals with immunological impairments.

“The rapid development and deployment of effective COVID-19 vaccines has been a triumph of biomedical research and has dramatically reduced the overall clinical severity of SARS-CoV-2 infection among vaccinees,” said researchers. “Mechanisms by which vaccines provide clinical protection are multifactorial, including antibodies that wane quickly following immunization and T-cells that are more durable and more cross-reactive against SARS-CoV-2 variants. The emergence of new SARS-CoV-2 variants continues to threaten vaccine efficacy, requiring constant reevaluation on how to optimize next-generation COVID-19 vaccines. Developing vaccine platforms that provide greater durability and that induce better mucosal immunity will be important for next-generation COVID-19 vaccines to protect against infection as well as severe disease.” 

Reference
Mahrokhian SH, Tostanoski LH, Vidal SJ, et al. COVID-19 vaccines: immune correlates and clinical outcomes. Human Vaccines & Immunotherapeutics. 2024;20(1). doi:10.1080/21645515.2024.2324549