Immunogenicity, clinical efficacy and safety of additional second COVID‐19 booster vaccines against Omicron and its subvariants: A systematic review

Abstract

The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID‐19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real‐world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID‐19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID‐19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID‐19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID‐19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.

Current German Recommendations and International Research on the Use of COVID-19 Boosters among Health Care Providers in 2024: A Narrative Review

“…COVID-19 boosters in these individuals aim to reduce their occupational risk of infection and transmission to vulnerable populations. Bivalent boosters may provide protection against hospitalisation and severe symptoms caused by various SARS-CoV-2 variants [ 7 , 8 , 26 , 27 , 28 ], particularly in individuals with “hybrid immunity” [ 1 , 2 , 3 , 4 , 5 , 7 , 8 ]. Such boosters can enhance both humoral and cellular immunity, decrease infection rates, and offer protection, especially for specific populations such as organ transplant recipients, dialysis patients, individuals with chronic renal disease, the elderly population, and immunocompromised individuals [ 7 ].…”

“…Additionally, both mRNA vaccine groups showed significant increases in neutralising antibodies (nAb) and T-cell responses after the fourth dose (7.32, 95% CI, 3.24–16.54; 6.22, 95% CI, 3.90–9.92). The study also reported that Spikevax induced higher antibody (Ab) titres than Comirnaty Original after the fourth dose [ 6 , 7 ].…”

“…When comparing the monovalent Moderna with the bivalent Moderna after 28 days of the fourth dose of the bivalent vaccine as a second booster, this exhibited significantly greater nAb titres against Omicron BA.1 and other variants (BA.4/5, alpha, beta, gamma, and delta), maintaining a safety and reactogenicity profile akin to that of the monovalent vaccine [ 7 , 8 ].…”

“…According to Section 22a of the German Infection Protection Law, foreign nationals residing in EU countries who have been vaccinated with vaccines not approved by the EU, such as Sinovac (Sinovac Biotech Ltd. SVA:NASDAQ GS, Beijing, China), Sinopharm (China National Pharmaceutical Group Co., Beijing, China), COVAXIN, (Bharat Biotech International Ltd., Turkapally, India), and Sputnik V (Russian Gamaleya Research Institute of Epidemiology and Microbiology), are required to repeat the EU-approved vaccination [ 2 ], even though some investigators found that the Sinopharm booster is safe and capable of rescuing immune signals and further strengthening the protective immune response by increasing nAb levels against some Omicron sublineages [ 7 , 9 ].…”

“…Additionally, both mRNA vaccine groups showed significant increases in neutralising antibodies (nAb) and T-cell responses after the fourth dose (7.32, 95% CI, 3.24-16.54; 6.22, 95% CI, 3.90-9.92). The study also reported that Spikevax induced higher antibody (Ab) titres than Comirnaty Original after the fourth dose [6,7]. When comparing the monovalent Moderna with the bivalent Moderna after 28 days of the fourth dose of the bivalent vaccine as a second booster, this exhibited significantly greater nAb titres against Omicron BA.1 and other variants (BA.4/5, alpha, beta, gamma, and delta), maintaining a safety and reactogenicity profile akin to that of the monovalent vaccine [7,8].…”