A lipid nanoparticle-based BNT162b2 vaccine encoding the full-length SARS-CoV-2 S protein is modified by two proline mutations to lock it in a prefusion form ^[1][26]. The efficacy trial included 43,548 participants who were randomized to receive the BNT162b2 vaccine or a placebo ^[1][26]. They concluded that in 16 years old and above, two doses of BNT162b2 inferred 95% protection against COVID-19 ^[1][26]. However, according to another pivotal study, four months after the second dose, efficacy declined by an average of 6% every two months, from 96.2% to 83.7% ^[2][58]. In addition, a new study suggests that two doses of the Pfizer-BioNTech vaccine were less effective against a more contagious strain. The Pfizer-BioNTech vaccine was 93.7% effective against the Alpha variant and 88.0% effective against the Delta variant when given in two doses ^[3][59]. The vaccine’s effectiveness against the Omicron variant was 65.5% from 2 to 4 weeks, dropping to 8.8% at ≥25 weeks after two Pfizer doses. The booster increased the vaccine’s effectiveness to 73.9% from 2 to 4 weeks, then declined to 64.4% from 5 to 9 weeks ^[4][60].

Moderna vaccine is an mRNA-based vaccine encapsulated in a lipid nanoparticle that encodes a full-length spike protein of the SARS-CoV-2 in a prefusion-stabilized conformation ^[5][61]. A phase III randomized trial was conducted at 99 different centers across the US, in which participants were assigned to receive two doses of the mRNA-1273 vaccine or a placebo. A 94.1% efficacy was achieved by the Moderna vaccine ^[6][62]. A study was conducted on 26,683 COVID-19-positive patients, 16% (Delta infection) and 84% (Omicron infection), and over 67,000 who tested negative ^[7][63]. They concluded that in those who received two doses of the Moderna vaccine, the effectivity was 44% against the Omicron variant until three months after vaccination, with a decline in effectivity afterward. However, after three doses, increased effectiveness was noticed (94% against Delta and 72% against Omicron) within two months of receiving the vaccine. For immunocompromised patients, the effectiveness was only 29% ^[7][63].

The viral vector vaccine, AstraZeneca, uses a harmless virus as a delivery mode to carry the genetic material of the surface spike protein of SARS-CoV-2. It allows the cells to activate the immune system when the body reencounters the disease ^[8][64]. The virus vector generally used is ChAdOx1, or adenovirus, a virus known to induce the common cold in chimpanzees. This virus is modified not to cause harm or infection to the human body ^[8][64]. Many trials were performed to study how effective the immune response of AstraZeneca is towards hospitalization and the reduction of the symptomatic effect of COVID-19. A phase III randomized trial in the US was conducted by comparing two doses of the AstraZeneca vaccine to the placebo group ^[9][65]. The vaccine showed 79% efficacy in preventing severe symptomatic events and 100% in reducing the number of infected patients admitted to the hospital.

Another study was performed in Canada after the appearance of new, more contagious variants of SARS-CoV-2, such as Delta and Gamma, to evaluate how effective the vaccine is in lowering the risk and improving protection against both variants. Results from the Canadian Immunization Research Network against symptomatic events caused by different variants showed that after one dose of the AstraZeneca vaccine, the efficacy was reduced to 70% and 72% for Delta and Alpha variants, respectively ^[10][66]. At the same time, it was decreased to 50% for Beta and Gamma variants. In addition, for hospitalization, the efficacy was reduced to 92% and 86% for Delta and Alpha variants, respectively ^[10][66].

Johnson & Johnson uses the same vaccine platform as AstraZeneca; the adenovirus is used as a vehicle to transport the genetic code of SARS-CoV-2 ^[11][67]. In clinical trials, a single dose of Johnson showed 66.3% effectiveness in preventing SARS-CoV-2 infection and 50% efficacy against symptomatic events ^[11][12][67,68]. Many studies suggested the need for Johnson & Johnson’s booster dose to strengthen the vaccine’s benefits. A recent study in South Africa demonstrated that a booster dose from Johnson & Johnson showed up to 85% effectiveness in reducing hospitalization ^[13][69]. Another study in the US showed that antibody titers increased four to six times after booster doses compared to a single dose of the vaccine ^[14][70].

Convidecia is a viral vector vaccine similar to those of AstraZeneca and Johnson & Johnson ^[15][71]. It is produced by genetic engineering using recombinant virus technology. The vaccine showed low efficacy in reducing the symptomatic events of COVID-19 in clinical trials compared to other vaccines. Its effectiveness ranged from 57.5 to 63.7%. The vaccine’s efficacy against severe COVID-19 ranged from 91.7% to 96% ^[15][16][17][71,72,73]. In the phase IV clinical trial, the company that developed the vaccine, CanSinoBio, suggested that a heterologous booster would give a better immune response as it would stimulate the body to produce more antibodies to fight the virus. The heterologous booster showed a six-fold increase in neutralizing antibodies compared to a homologous booster dose ^[18][74]. Another study was performed using a protein subunit vaccine (ZF2001) as a heterologous booster compared to a homologous booster of Convidicea that showed from a 2.5- to 3.3-fold increase in humoral immune response and was safer and more tolerable ^[19][75].

Sinovac vaccine follows the usual platform used for vaccination using an inactivated virus. The WHO follow-up on the immunogenicity of Sinovac in human clinical trials showed that adults aged 18 and above could be immunized using Sinovac in two doses ^[20][76]. However, the antibodies formed from the two doses usually decline after three months ^[20][76]. Moreover, a study in Chile on the age group of 60 years and older showed that the vaccine was 66.6%, 85.3%, and 89.2% effective against COVID-19 infection, hospitalization, and ICU admission, respectively ^[21][77]. For adults between 18 and 59 years old, the efficacy in preventing COVID-19 infection was 65.03% ^[22][78]. Another study showed that antibodies formed after two doses of Sinovac were significantly lower in older patients, with an average of 85.3% efficacy compared to adults with an efficacy of 97.4% ^[23][79].

Like Sinovac, Sinopharm is also an inactivated vaccine ^[24][80]. In 2021, WHO approved the Sinopharm vaccine for emergency use based on interim phase III clinical trial data since it prevents symptomatic diseases in 79% of cases in adults younger than 60 years old ^[25][81]. Additionally, participants in the phase III clinical trial were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 and HB02 strains or a placebo. During an average follow-up duration of 77 days for WIV04, the vaccine efficacy was 72.8%, and for HB02, it was 78.1%. They reported only two severe cases in the placebo group ^[26][82]. A case-control study of vaccinated elderly individuals showed that 14 days after the second dose, the Sinopharm vaccine reduced the risk of symptomatic COVID-19 infection, hospitalizations, and mortality by 94.3%, 60.5%, and 98.6%, respectively ^[27][83].

The last WHO-approved inactivated vaccine for emergency use was Covaxin. During the phase III trial in India, Covaxin showed 81% efficacy against SARS-CoV-2 infection ^[28][84]. However, another study was performed to determine the effectiveness of Covaxin against the Delta variant. The efficacy of the vaccine was 64% after two doses and 44% after one dose, respectively ^[29][85]. This can conclude that Covaxin is a moderately effective vaccine, but it might not fully protect individuals against the new mutant strains. Additionally, a study showed that after six months of the first and second doses of Covaxin, the seropositivity was reduced significantly in individuals aged 60 years and older compared to younger individuals. Furthermore, the vaccine-induced antibody titers, regardless of age, were decreased after 6 months of vaccination by 56% ^[30][86].

Covovax is the only protein subunit vaccine approved for emergency use in COVID-19. In India, the Covovax vaccine was given to individuals who were 18 years old and above, but recently it has been approved to be given to children from 12 to 17 years old ^[31][87]. In the phase III trial in India, the vaccine showed 89.3% effectiveness against COVID-19 infection ^[32][88]. In addition, a study in the UK comparing the Covovax vaccine with a placebo revealed that the vaccine was 86.3% and 96.4% effective against Alpha and non-Alpha variants, respectively, with no reported hospitalizations or deaths after immunization ^[33][29]. Briefly, all WHO-approved COVID-19 vaccines reduced symptoms of infection and prevented complications associated with them.