• Manufacturer: Academy of Military Science (AMS), Walvax Biotechnology, Suzhou Abogen Biosciences
• Vaccine Ontology ID: VO_0005161
• Type: mRNA vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: mouse, cynomolgus monkeys
• Antigen: RBD domain of S protein (Zha, et al., 2020)
• Vector: Lipid nanoparticles (Zha, et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Storage: After treament can store
• Description: A SARS-CoV-2 mRNA vaccine made of lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2
  (Zha, et al., 2020)

• Manufacturer: Beijing Institute of Biological Products, Sinopharm
• Vaccine Ontology ID: VO_0005167
• Type: Inactivated or "killed" vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Antigen: whole virus
• Immunization Route: Intramuscular injection (i.m.)
• Description: An inactivated whole virus vaccine produced in Vero cells.

• Product Name: BNT162b2
• Manufacturer: Pfizer, BioNTech
• Vaccine Ontology ID: VO_0004987
• CDC CVX code: 208
• CDC CVX description: SARS-COV-2 (COVID-19) vaccine, mRNA, spike protein, LNP, preservative free, 30 mcg/0.3mL dose
• Type: mRNA vaccine
• Status: Licensed
• Host Species for Licensed Use: Human
• Antigen: trimerized SARS-CoV-2 receptor-binding domain from S
• Vector: Lipid nanoparticle
• Immunization Route: Intramuscular injection (i.m.)
• Storage: -70°C ±10°C
• Description: A SARS-CoV-2 RNA vaccine formed from a lipid nanoparticle-formulated trimerized SARS-CoV-2 receptor-binding domain

• Product Name: PiCoVacc
• Manufacturer: Sinovac Biotech Ltd
• Vaccine Ontology ID: VO_0005142
• Type: Inactivated or "killed" vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Mouse, Macaque, Rat
• Antigen: Whole virus (Gao et al., 2020)
• Preparation: The virus was propagated in a 50-liter culture of Vero cells using the Cell Factory system and inactivated by using β-propiolactone The virus was purified using depth filtration and two optimized steps of chromatography, yielding a highly pure preparation of PiCoVacc. (Gao et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A purified inactivated SARS-CoV-2 virus vaccine(Gao et al., 2020)

• Product Name: BBV152
• Manufacturer: Bharat Biotech
• Vaccine Ontology ID: VO_0004991
• Type: Inactivated or "killed" vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Adjuvant:
  • VO ID: VO_0005301
• Preparation: COVAXIN is made up of an inactivated SARS-CoV-2 virus that activates the immune system to create antibodies againt the virus. When preparing the vaccine, Beta-propiolactone, an organic compound, inactivates the virus by binding to its genes. The vaccine itself contains the RNA of the virus surrounded by a protein shell that cannot be replicated. It also contains an adjuvant, Alhydroxiquim-II, which includes a molecule attached to Alhydrogel (alum used in many adjuvants). After injection of the vaccine, the adjuvant moves to the lymph nodes, where it separates from the alum and attaches to two cell receptors, activating a TLR7/8 agonist and Th1 immune system response. The virus contains a receptor on its outer-shell which is adsobrded to the adjuvant. (Ella et al., 2021; LABline, 2021; Thiagarajan, 2021)
• Immunization Route: Intramuscular injection (i.m.)

• Product Name: Ad26.COV2.S
• Tradename: JNJ-78436735
• Manufacturer: Janssen Pharmaceutica
• Vaccine Ontology ID: VO_0005159
• CDC CVX code: 212
• CDC CVX description: SARS-COV-2 (COVID-19) vaccine, vector non-replicating, recombinant spike protein-Ad26, preservative free, 0.5 mL
• Type: Recombinant vector vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: macaques
• Antigen: S protein with tissue plasminogen activator leader sequence and two proline stabilizing mutations (Mercado et al., 2020)
• spike (S) protein gene engineering:
  • Type: Recombinant vector construction
  • Description: The S protein gene is engineered to be added to the Ad viral vaccine vector for expression (Mercado et al., 2020).
  • Detailed Gene Information: Click Here.
• Vector: adenovirus serotype 26 (Ad26) (Mercado et al., 2020)
• Immunization Route: intranasal immunization
• Description: A recombinant viral vector virus using adenovirus serotype26 vector experssing the S protein (Mercado et al., 2020).
  Ad26.COV2.S is currently undergoing a Phase III clinical trial: (NCT04505722)

• Product Name: mRNA-1273
• Manufacturer: Moderna
• Vaccine Ontology ID: VO_0005157
• CDC CVX code: 207
• CDC CVX description: SARS-COV-2 (COVID-19) vaccine, mRNA, spike protein, LNP, preservative free, 100 mcg/0.5mL dose
• Type: mRNA vaccine
• Status: Licensed
• Host Species for Licensed Use: Human
• Antigen: S-2P antigen, made of the SARS-CoV-2 glycoprotein with a transmembrane anchor and intact S1-S2 cleavage site (Wang et al., 2020).
• Vector: lipid nanoparticle (Wang et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A SARS-CoV2 RNA vaccine made of lipid nanoparticle with mRNA which encodes the S-2P antigen, made of the SARS-CoV-2 glycoprotein with a transmembrane anchor and intact S1-S2 cleavage site (Wang et al., 2020).

• Product Name: ChAdOx1 nCoV19 vaccine
• Tradename: AZD1222
• Manufacturer: AstraZeneca
• Vaccine Ontology ID: VO_0005158
• CDC CVX code: 210
• CDC CVX description: SARS-COV-2 (COVID-19) vaccine, vector non-replicating, recombinant spike protein-ChAdOx1, preservative free, 0.5 mL
• Type: Recombinant vector vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Antigen: SARS-CoV-2 spike protein (Folegatti et al., 2020)
• Vector: chimpanzee adenovirus-vectored vaccine (ChAdOx1) (Folegatti et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein (Folegatti et al., 2020)

Human Response

• Vaccination Protocol: Participants 19-55 years of age were vaccinated with BNT162b2 in Germany. Twelve participants per dose cohort were assigned to receive a priming dose of 1, 10, 20 or 30 μg on day 1 and a booster dose on day 22. (Sahin et al., 2020)
• Immune Response: BNT162b2 elicited strong antibody responses, with S-binding IgG concentrations above those in a COVID-19 human convalescent sample (HCS) panel. Day 29 (7 days post-boost) SARS-CoV-2 serum 50% neutralising geometric mean titers were 0.3-fold (1 µg) to 3.3-fold (30 µg) those of the HCS panel. The BNT162b2-elicited sera neutralized pseudoviruses with diverse SARS-CoV-2 S variants. In most participants, S-specific CD8+ and T helper type 1 (TH1) CD4+ T cells had expanded, with a high fraction producing interferon-γ (IFNγ). CD8+ T cells were shown to be of the early-differentiated effector-memory phenotype, with single specificities reaching 0.01-3% of circulating CD8+ T cells. Vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19. (Sahin et al., 2020)
• Side Effects: No serious adverse events (SAE) and no withdrawals due to related adverse events (AEs) were observed at any dose level. Local reactions, predominantly pain at the injection site, were mild to moderate (grade 1 and 2) and were similar in frequency and severity after the priming and booster doses. The most common systemic AEs were fatigue followed by headache and only two participants reported fever, which was mild. Transient chills were more common after the boost, dose-dependent, and occasionally severe. Muscle pain and joint pain were also more common after the boost and showed dose-dependent severity. There were no grade 4 reactions. Generally, reactions had their onset within 24 hours of immunisation, peaked on the day after immunisation, and mostly resolved within 2-3 days. Reactions did not require treatment or could be managed with simple measures (e.g. paracetamol). (Sahin et al., 2020)

Human Response

• Vaccination Protocol: A double-blind, multicentre, randomised, controlled phase 1 trial was conducted to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18–55 years who were deemed healthy by the investigator were eligible. The vaccine candidates were formulated with two adjuvants: Algel (alum) and Algel-IMDG, an imidazoquinoline class molecule (TLR7 and TLR8 agonist) adsorbed onto Algel. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. The vaccine (BBV152) and the control were provided as a sterile liquid that was injected intramuscularly (deltoid muscle) at a volume of 0·5 mL/dose in a two-dose regimen on day 0 (day of randomisation) and day 14. [Ella et al., 2021]
• Immune Response: IgG titres (GMTs) to all epitopes (spike protein, receptor-binding domain, and nucleocapsid protein) increased rapidly after the administration of both doses. Both 3 μg and 6 μg with Algel-IMDG groups reported similar anti-spike, anti-receptor binding, and anti-nucleoprotein IgG titres (GMTs), adding to the dose-sparing effect of the adjuvant. The mean isotyping ratios (IgG1/IgG4) were greater than 1 for all vaccinated groups, which was indicative of a Th1 bias. Seroconversion rates (after the second dose), based on MNT50 were 87·9% (95% CI 79·8–94·3) in the 3 μg with Algel-IMDG group, 91·9% (84·6–96·0) in the 6 μg with Algel-IMDG group, and 82·8% (73·7–89·2) in the 6 μg with Algel group. Seroconversion (at day 28) in the control group was reported in six (8% [3·6–17·2]) of 75 participants, suggestive of asymptomatic infection. The vaccine-induced responses were similar to those observed in the convalescent serum collected from 41 patients who had recovered from COVID-19 (figure 3B). On these 41 patients, the median titre of symptomatic patients (n=25; median 142·2 [IQR 56·6–350]) was significantly higher than that of the asymptomatic patients (n=16; 22·6 [9·0–56·5]).Randomly selected serum samples from day 28 were analysed by PRNT50 at the National Institute of Virology with homologous and heterologous strain assessments. Neutralisation responses, regardless of the challenge strain, were observed. In a subset of randomly selected blood samples at one site, IFN-γ ELISpot responses against SARS-CoV-2 peptides peaked at about 100–120 spot-forming cells per million peripheral blood mononuclear cells in all vaccinated groups on day 28. Both the Algel-IMDG groups elicited CD3+, CD4+, and CD8+ T-cell responses that were reflected in the IFN-γ production, albeit in a small number of samples. However, there was a minimal detection of less than 0·5% of CD3+, CD4+, and CD8+ T-cell responses in the 6 μg with Algel group and the Algel only group. [Ella et al., 2021]
• Efficacy: Because this is an interim report, we are not reporting any data on the persistence of vaccine-induced antibody responses or long-term safety outcomes. The results reported here do not permit efficacy assessments. The analysis of safety outcomes requires more extensive phase 2 and 3 clinical trials. [Ella et al., 2021]

Human Response

• Vaccination Protocol: All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. (Anderson et al., 2020) The mRNA-1273 vaccine was administered as a 0.5-ml intramuscular injection into the deltoid on days 1 and 29 of the study.
• Immune Response: By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. (Anderson et al., 2020)
• Side Effects: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. (Anderson et al., 2020)

Human Response

• Vaccination Protocol: Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. (Folegatti et al., 2020)
• Immune Response: In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). (Folegatti et al., 2020)
• Side Effects: Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. (Folegatti et al., 2020)

Mouse Response

• Vaccination Protocol: Female BALB/c mice were immunized i.m. with 2 μg (n = 8) or 10 μg (n = 8) of ARCoV or a placebo (n = 5) and boosted with an equivalent dose 14 days later. Serum was collected 7, 14, 21, and 28 days after initial vaccination. (Zhang et al., 2020)
• Immune Response: Remarkably, a second immunization with 2 or 10 μg of ARCoV mRNA-LNP resulted in rapid elevation of immunoglobulin G (IgG) and neutralizing antibodies in mice, whereas no SARS-CoV-2-specific IgG and neutralizing antibodies were detected in sera from mice vaccinated with empty LNPs. 28 days after initial immunization, the NT50 titers in mice immunized with 2 or 10 μg of ARCoV mRNA-LNP approached ∼1/2,540 and ∼1/7,079, respectively, and the PRNT50 reached ∼1/2,194 and ∼1/5,704, respectively. (Zhang et al., 2020)
  There was a significant increase in virus-specific CD4+ and CD8+ effector memory T (Tem) cells in splenocytes from ARCoV-vaccinated mice in comparison with placebo LNPs (Figure 4 A) upon stimulation with peptide pools covering the SARS-CoV-2 RBD. Secretion of interferon γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) in splenocytes from mRNA-LNP-immunized mice was significantly higher than in those that received the placebo vaccination. There was no significant difference in IL-4 and IL-6 secretion between ARCoV-immunized animals and placebo-immunized ones, demonstrating that the mRNA-LNP vaccine successfully induces a Th1-biased, SARS-CoV-specific cellular immune response. (Zhang et al., 2020)
• Challenge Protocol: Mice that received two doses of immunization of ARCoV mRNA-LNP at 2 or 10 μg were challenged i.n. with 6,000 plaque-forming units (PFUs) of SARS-CoV-2 MASCp6 40 days after initial vaccination. (Zhang et al., 2020)
• Efficacy: All mice immunized with 2 or 10 μg of ARCoV mRNA-LNP showed full protection against SARS-CoV-2 infection, and no measurable viral RNA was detected in the lungs and trachea , whereas high levels of viral RNA were detected in the lungs and trachea (∼109 and 107 RNA copy equivalents per gram, respectively) of mice in the placebo group. (Zhang et al., 2020)

Mouse Response

• Host Strain: BALB/c mouse
• Vaccination Protocol: Mice were vaccinated at day 0 and 7 with either 1.5 μg/dose, 3.0 μg/dose, or 6.0 μg/dose on both days. (Gao et al., 2020)
• Immune Response: SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated mice and peaked at the titer of 819,200 (>200 μg/ml) and 409,600 (>100 μg/ml), respectively, at week 6(Gao et al., 2020)
• Description: BALB/c mice were injected with vaccine 5761 at days 0 and 7.(Gao et al., 2020)

Rat Response

• Host Strain: Wistar
• Vaccination Protocol: Rats were vaccinated at day 0 and 7 with either 1.5 μg/dose, 3.0 μg/dose, or 6.0 μg/dose on both days.(Gao et al., 2020)
• Immune Response: Immune Response Description: SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated rats and the maximum neutralizing titers reached 2,048-4,096 at week 7 (Gao et al., 2020)

Macaque Response

• Vaccination Protocol: Two groups of macaques (n = 10/group) were immunized with 100 or 1,000 μg of ARCoV mRNA-LNP via i.m. administration and boosted with the same dose 14 days after initial immunization. The same number of monkeys (n = 10) was vaccinated with PBS as a placebo. (Zhang et al., 2020)
• Immune Response: specific IgG antibodies were readily induced on day 14 after initial immunization, and the booster immunization resulted in a notable increase in IgG titers to ∼1/5,210 and ∼1/22,085 on day 28 after initial immunization. Fifty percent of animals that received high-dose ARCoV immunization developed low-level neutralizing antibodies on day 14 after initial immunization, whereas the booster immunization resulted in a notable increase in NT50 to ∼1/699 and ∼1/6,482 in monkeys vaccinated with low- or high-dose ARCoV, respectively. SARS-CoV-2 RBD-specific T cell responses were stimulated in peripheral blood monocytes (PBMCs) from monkeys vaccinated with a low or high dose of ARCoV on day 5 after booster immunization but not from animals receiving a placebo. There was no significant difference in IL-4+/CD4+ cell response to the SARS-CoV-2 RBD between ARCoV- and placebo-treated animals, suggesting induction of a Th1-biased cellular immune response by ARCoV immunization. (Zhang et al., 2020)

Macaque Response

• Vaccination Protocol: All macaques were immunized twice on days 0 (D0) and 14 (D14). The placebo group was intramuscularly administered physiological saline, and the two experimental groups were intramuscularly injected with low-dose (2 μg/dose) or high-dose (8 μg/dose) BBIBP-CorV. (Wang et al., 2020)
• Immune Response: Before virus challenge at D24, the geometric mean titer of neutralizing antibodies in the low-dose and high-dose groups reached 215 and 256, respectively. (Wang et al., 2020)
• Challenge Protocol: At D24 (10 days after the second immunization), all macaques were intratracheally challenged with l06 TCID50 of SARS-CoV-2 per monkey under anesthesia. (Wang et al., 2020)
• Efficacy: All placebo macaques showed and maintained a high viral load during the whole evaluation period after virus challenge by both throat and anal swabs. In contrast, the viral load in the throat swabs of the low-dose group peaked (5.33 log10copies/mL) at 5 dpi and then decreased to 1.12 log10copies/mL at 7 dpi, which was significantly lower than that of the placebo group. Moreover, no viral load was detected in the anal swabs of two (out of four) macaques in the high-dose group. (Wang et al., 2020) No macaques in the low-dose and high-dose groups had a detectable viral load in any lung lobe, which was significantly different from the results in the placebo group. Furthermore, all macaques that received vaccination showed normal lung with focal mild histopathological changes in few lobes, demonstrating the BBIBP-CorV vaccination could efficiently block the infection of SARS-CoV-2 and COVID-19 disease in monkey. At 7 dpi, the macaques treated with placebo produced low-level NAb with a titer of 1:16, whereas the NAb levels of the vaccinated macaques were highest at 1:2,048 (average 1:860) in the high-dose group and 1:1,024 in the low-dose group (average 1:512). Taken together, all these results demonstrated that both low-dose and high-dose BBIBP-CorV conferred highly efficient protection against SARS-CoV-2 in macaques without observed antibody-dependent enhancement of infection. (Wang et al., 2020)

Macaque Response

• Vaccination Protocol: Groups of six male, 2-4 year old rhesus macaques were immunized IM with 30 or 100 μg of BNT162b2 or saline control on Days 0 and 21. (Vogel et al., 2020)
• Immune Response: Seven days after Dose 2 (Day 28), the GMCs of S1-binding IgG were 30,339 units (U)/mL (30 μg dose level) and 34,668 U/mL (100 μg dose level). Fifty percent virus neutralisation GMTs, measured by an authentic SARS-CoV-2 neutralisation assay25, were detectable in rhesus macaque sera by Day 21 after Dose 1 and peaked at a GMT of 962 (Day 35, 14 days after Dose 2 of 30 μg) or 1,689 (Day 28, 7 days after Dose 2 of 100 μg; Fig. 3b). Robust GMTs of 285 for 30 μg and 310 for 100 μg dose levels persisted to at least Day 56. Strong IFNγ but minimal IL-4 responses were detected by ELISpot after Dose 2. BNT162b2 elicited strong S-specific IFNγ producing T-cell responses, including a high frequency of CD4+ T cells that produced IFNγ, IL-2, and TNF but a low frequency of CD4+ T cells that produced IL-4, indicating a TH1-biased response. BNT162b2 also elicited S-specific IFNγ+ producing CD8+ T cells. (Vogel et al., 2020)
• Challenge Protocol: Six rhesus macaques that had received two immunisations with 100 μg BNT162b2 and three age-matched macaques that had received saline were challenged 55 days after Dose 2 with 1.05 × 106 plaque forming units of SARS-CoV-2 (strain USA-WA1/2020), split equally between intranasal and intratracheal routes. Three additional non-immunised, age-matched rhesus macaques (sentinels) were mock-challenged with cell culture medium. (Vogel et al., 2020)
• Efficacy: BNT162b2 immunization prevented lung infection in 100% of the SARS-CoV-2 challenged rhesus macaques, with no viral RNA detected in the lower respiratory tract of immunized and challenged animals. The BNT162b2 vaccination also cleared the nose of detectable viral RNA in 100% of the SARS-CoV-2 challenged rhesus macaques within 3 days after the infection. (Vogel et al., 2020)

Macaque Response

• Host Strain: Rhesus macaque
• Vaccination Protocol: Macaques were immunized three times via the intramuscular route with medium (3 μg per dose) or high doses (6 μg per dose) of PiCoVacc at day 0, 7 and 14 (n=4)(Gao et al., 2020)
• Immune Response: . S-specific IgG and NAb were induced at week 2 and rose to ~12,800 and ~50, respectively at week 3 after vaccination in both vaccinated groups, whose titers are similar to those of serum from the recovered COVID-19 patients. NAb titer (61) in the medium dose immunized group were ~20% greater than that observed (50) in the high dose vaccinated group at week 3, removing the outlier instead have medium dose group be ~40% lower than that in the high dose group (Gao et al., 2020)
• Side Effects: No serious pathology recorded at day 29 in vaccinated groups (Gao et al., 2020)
• Challenge Protocol: Challenge protocol involved direct inoculation of 1e6 TCID50 of SARS-CoV-2 CN1 into the animal lung through the intratracheal route at day 22 (one week after the third immunization and after immune response results were recorded) (Gao et al., 2020).
• Efficacy: argely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung, which probably were caused by a direct inoculation of 106 TCID50 of virus into the lung through intratracheal route, that needed longer time (more than one week) to recover completely (Gao et al., 2020).

Macaque Response

• Vaccination Protocol: Twenty adult rhesus macaques aged 3 - 12 years were divided into 4 groups of five animals (3 M, 2 F) each viz. the placebo (group I), group II, III, and IV. The placebo group was administered Phosphate buffer saline (PBS), group II, III, and IV were immunized with formulations of purified inactivated SARS-CoV-2 vaccine candidate 6μg+Adjuvant-A(BBV152C), 3μg+Adjuvant-B (BBV152A), and 6μg+Adjuvant-B (BBV152B) respectively. Animals were administered with two doses of vaccine/placebo on days 0 and 14 respectively intramuscularly in the deltoid region. Blood samples were collected on 0, 12, 19, 26, and 28 days for assessing the anti-SARS IgG antibody and NAb titers.
• Immune Response: We evaluated anti-SARS-CoV-2 Immunoglobulin-G (IgG) antibody and neutralizing antibody (NAb) titers from the serum samples during the immunization phase (0, 12, 19, 26 and 28 days) and after SARS-CoV-2 infection (0, 1, 3, and 7). IgG levels were detectable from 3rd-week post-immunization and were found increasing till 35th day [7 days post-infection (DPI)]. Group III showed the highest IgG titer (1:25600) compared to group II and IV (1:1600-1:6400). The highest NAb titers of 1:209 to 1:5,217 were detected in group III after the SARS-CoV-2 challenge. The NAb titers for groups II and IV were (1:87.4 - 1: 3974) and (1:29.5 -1: 3403) respectively. These NAb titers correlated with the IgG antibody titers. NAb and IgG response was not detectable in the placebo group.
• Side Effects: Adverse events were not seen in animals immunized with a two-dose vaccination regimen.
• Challenge Protocol: After completion of twenty eight-days of immunization, animals were challenged with 1 ml of SARS-CoV-2 (P-3, NIV-2020770, TCID50 106.5/ml)19 intratracheally and 0.25 ml in each nostril. NS, TS, rectal swab, chest X-ray, blood specimens, and BAL fluid were collected on 0, 1, 3, 5, and 7 DPI.
• Efficacy: Vaccinated groups had a detectable level of gRNA from 1 to 5 DPI with viral clearance on 7 DPI (Figure 2B). sgRNA was not detected in TS specimens of animals from either group. In the vaccinated groups, gRNA was detected in BAL specimens until 3 DPI (Figure 2C). sgRNA was detected in BAL specimens of four out of five animals of the placebo group, while it was not detected in BAL specimens of vaccinated groups. Except for the placebo group, none of the vaccinated groups showed the presence of gRNA in lung lobes (Figure 2D). The comparisons of viral copy numbers of the NS, TS, and the BAL fluid samples of the vaccinated as compared to the placebo group were found to be statistically significant using the two-tailed Mann-Whitney test.

Macaque Response

• Vaccination Protocol: Immunized vector with Ad26 vaccine with immunization of 10^11 viral particles by the intramuscular route on week 0.
• Immune Response: Liver titer neutralizing antibodies present (median 113; range 53-233) (Mercado et al., 2020). Presence of INF-gamma response but minimal to no IL-4 response (Mercado et al., 2020). NAb titers as measured by both assays were observed in the majority of vaccinated animals at week 2 and generally increased by week 4. The Ad26-S.PP vaccine elicited the highest pseudovirus NAb titers (median 408; range 208–643) and live virus NAb titers (median 113; range 53–233) at week 4. The Ad26-S.PP vaccine also induced detectable S-specific IgG and IgA responses in bronchoalveolar lavage (BAL). Cellular immune responses were induced in 30 of 32 vaccinated animals at week 4. A single immunization of 1011 vp Ad26-S.PP elicited consistent IFN-γ ELISPOT responses but minimal to no IL-4 ELISPOT responses, suggesting induction of Th1-biased responses. (Mercado et al., 2020)
• Challenge Protocol: Week 6 after initial vaccination had each animal exposed to 1^4 TCID50 SARS-CoV2 vy the intranasal and intratracheal routes (Mercado et al., 2020).
• Efficacy: Complete protection called due to no detecable vius in bronchoalveolar lavage with limit of detectin of 1.69log10sgRNAcopies/Ml (Mercado et al., 2020). Macaques that were treated with Ad26-S.PP had no detectable virus in BAL samples. Only one of the macaques that received the Ad26-S.PP vaccine showed a low amount of virus in nasal swabs. All vaccinated macaques showed no detectable infectious virus in nasal swabs by plaque-forming unit (PFU) assays. A comparison of peak viral loads in the vaccinated macaques suggested that protection in BAL samples was generally more robust than in nasal swabs (Fig. 5). The Ad26-S.PP vaccine provided complete protection in both the lower and upper respiratory tract with the exception of one macaque that showed a low amount of virus in nasal swabs, and resulted in greater than 3.2 and 3.9 log10-transformed reductions of median peak sgRNA in BAL and nasal swabs, respectively, as compared with sham controls (P < 0.0001 and P < 0.0001, respectively, two-sided Mann–Whitney tests) (Fig. 5). Among the 32 vaccinated macaques, 17 were completely protected and had no detectable sgRNA in BAL or nasal swabs after challenge, and 5 additional macaques had no sgRNA in BAL but showed some virus in nasal swabs. (Mercado et al., 2020)

Macaque Response

• Vaccination Protocol: Animals were vaccinated intramuscularly at week 0 and at week 4 with either 10 or 100 μg of mRNA-1273 in 1 ml of 1× phosphate-buffered saline (PBS) into the right hind leg. (Corbett et al., 2020)
• Immune Response: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. (Corbett et al., 2020)
• Challenge Protocol: At week 8 (4 weeks after the second vaccination), all animals were challenged with a total dose of 7.6×105 plaque-forming units (PFU). The stock of 1.9×105 PFU per milliliter SARS-CoV-2 (USA-WA1/2020 strain) was administered in a volume of 3 ml by the intratracheal route and in a volume of 1 ml by the intranasal route (0.5 ml per nostril). (Corbett et al., 2020)
• Efficacy: Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. (Corbett et al., 2020)

Macaque Response

• Vaccination Protocol: Six animals per group were vaccinated using a prime-only regimen (28 days before challenge) or a prime–boost regimen (56 and 28 days before challenge) intramuscularly with 2.5 × 1010 ChAdOx1 nCoV-19 virus particles each. As a control, six animals were vaccinated via the same route with the same dose of ChAdOx1 GFP. (van et al., 2020)
• Immune Response: Spike-specific antibodies were present as early as 14 days after vaccination and were significantly increased after the second immunization. Endpoint IgG titres of 400–6,400 (prime) and 400–19,200 (prime–boost) were measured on the day of challenge. Virus-specific neutralizing antibodies were also significantly increased after secondary immunization and detectable in all vaccinated animals before challenge (5–40 (prime) and 10–160 (prime–boost)), whereas no virus-specific neutralizing antibodies were detected in control animals. IgM antibodies were present in the serum after vaccination on the day of the challenge in six out of six prime–boost and two out of six prime-only animals. SARS-CoV-2 spike-specific T cell responses were detected on the day of challenge. No statistically significant difference in the magnitude of the response was found between the prime–boost and prime-only group. Vaccination with ChAdOx1 nCoV-19 resulted in the induction of neutralizing antibodies against the vaccine vector itself within 28 days of vaccination. A boost vaccination with ChAdOx1 nCoV-19 resulted in a significant increase in binding and neutralizing antibodies in NHPs and an increase in the SARS-CoV-2 virus-neutralizing titre was not significantly correlated with the ChAdOx1 virus-neutralizing titre. (van et al., 2020)
• Side Effects: No adverse events were observed after vaccination. (van et al., 2020)
• Challenge Protocol: Rhesus macaques were challenged with a 50% tissue culture infective dose (TCID50) of 2.6 × 106 of SARS-CoV-2 in both the upper and lower respiratory tracts.
• Efficacy: Viral gRNA and sgRNA were detected in only two vaccinated animals on 3 d.p.i., and the viral load was significantly lower. Viral gRNA was detected in nose swabs from all animals and no difference was found on any day between vaccinated and control animals. Viral sgRNA was detected in a minority of samples, with no difference between groups. Infectious virus could only be detected at 1 and 3 d.p.i. in prime-only vaccinated and control animals, and 1 d.p.i. in prime–boost vaccinated animals. (van et al., 2020)