The NVX-CoV2373 vaccine found to be effective for preventing mild to moderate COVID-19 caused by B.1.351 variant. 

COVID-19 outbreak due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of death globally. The emerging variants of SARS-CoV-2 are alarming and pose a threat in the control of this deadly pandemic. For managing coronavirus-infected patients, vaccination is an important approach with the current vaccines majorly targeting the coronavirus spike protein based on the prototype Wuhan strain.

In patients with coronavirus infection (of any severity), the mRNA vaccines such as mRNA-1273 and BNT162b2 have shown efficacy of 94-95%. On the other hand, the efficacy of vector-based vaccines has been witnessed to be 67% for Ad26.COV2.S, 70% (pooled) for ChAdOx1-nCoV19, and 92% for Gam-COVID-Vac against moderate to severe coronavirus infection.

NVX-CoV2373 is a recombinant SARS-CoV-2 nanoparticle vaccine. Derived from Spodoptera frugiperda insect cell/baculovirus system and co-formulated with a saponin-based adjuvant Matrix-M1,  it consists of full-length, pre-fusion trimers of spike glycoprotein (prototype Wuhan sequence).

In healthy adults, this investigational vaccine given in a two-dose regimen 21 days apart illustrated an acceptable safety profile in an ongoing phase 1/2, randomized, placebo-controlled clinical trial
It was found to be linked with a strong, antigen-specific polyfunctional CD4+ T-cell response. Also, it was reported to stimulate neutralizing antibody responses four-fold greater than levels in the convalescent sera from moderate to severe SARS-CoV-2 cases.

Recently, there have been reports of emerging N501Y.V2 variants in Brazil (P1), South Africa (B.1.351), and the United Kingdom (B.1.1.7). This illustrates the acquisition of mutations in the vital antigenic sites in the receptor binding and N-terminal domain of the spike protein. Such antigenic modifications may cause naturally acquired or vaccine-derived immunity to prototype-like viruses less effective against the subsequent exposure to the variant viruses.

Rationale behind research

Assessment of COVID-19 vaccine efficacy against SARS-CoV-2 variants is immediately required for the development and utilization of the vaccine. Thus, this study was performed.

Objective

This study aimed to describe the early findings on the primary efficacy and safety outcome of a phase 2a–b, observer-blinded, randomized, placebo-controlled trial of nanoparticle vaccine NVX-CoV2373 against B.1.351 variant virus. 

Study outcomes

• The major endpoints were the safety and efficacy of the vaccine against lab-confirmed symptomatic coronavirus infection at 7 days or more following the second dose in individuals without prior SARS-CoV-2 infection.   

Outcomes

Baseline: About 30% of people were noted to be seropositive for SARS-CoV-2 at baseline.

Study outcomes

• In 2684 baseline seronegative people (6% people living with HIV, 94% HIV-negative), about 15 vaccine recipients and 29 placebo patients developed mild to moderate SARS-CoV-2 cases (Figure 2)
• The vaccine efficacy was found to be 49.4% in all patients and 60.1% in HIV-negative subjects
• Among 41 sequenced isolates, 92.7% (38/41) were B.1.351 variant
• The post-hoc vaccine efficacy against B.1.351 was 51% in HIV-negative people
• The preliminary local and systemic reactogenicity were principally mild to moderate and transient, and greater with the investigational vaccine; severe side effects were rare in both  arms

This study aimed to elucidate the preliminary evidence of the efficacy of prototype-sequenced NVX-CoV2373 to prevent symptomatic coronavirus infection during transmission of the B.1.351 variant. NVX-CoV2373 (5 μg recombinant spike protein with 50 μg Matrix-M1 adjuvant) displayed an efficacy of 49.4% in people seronegative for coronavirus at baseline irrespective of HIV serostatus. The efficacy of the vaccine was reported to be 60.1% in 94% of participants without HIV.

This analysis was not powered for detecting efficacy in the small population of people suffering from HIV. The preliminary safety data indicated an acceptable reactogenicity and safety profile of the vaccine. Thus, in the setting of a controlled vaccine trial, previous infection with the first-wave prototype-like, pre-B.1.351 viruses did not seem to minimize the risk of SARS-CoV-2 due to re-infection with B.1.351 variants in patients given a placebo during the initial two months of follow-up. This preliminary outcome may have public health implications for control strategies, pandemic modeling, development of the vaccine, and deployment efforts.

These results are consistent with the paucity of an incremental advantage conferred by pre-existing immunity in people receiving the vaccine as affirmed by consistent levels of efficacy irrespective of baseline serostatus. Though the findings need further confirmation, the observations indicate that vaccination with NVX-CoV2373 exhibited cross-protection against the variant.

The B.1.351 variant, characterized by 3 detrimental mutations at main antigenic sites in the receptor-binding domain, including N501Y, K417N, and E484K, has expeditiously spread to become the dominant circulating strain. Mutations in K417N and E484K exhibit a specific functional impact. The N501Y mutation has been observed to raise the transmissibility of the B.1.17 variant circulating and is well-known for increasing the binding affinity of spike protein to the human angiotensin-converting enzyme 2 receptor.

The E484K mutation considerably decreases neutralization by multiple potent monoclonal antibodies and polyclonal convalescent sera in both pseudo-virus and wild-type neutralization assays. Furthermore, post-vaccination sera derived from subjects given either of the mRNA vaccines demonstrated a 6.5- to 8.6-fold decline in neutralizing capacity to the B.1.351 variant relative to prototype virus in pseudovirus neutralization.

But, the impact on clinical efficacy is still not clear. The wild-type and pseudo-virus neutralization assays exploring the influence of the B.1.351 variant on the neutralizing capacity of nanoparticle vaccine-stimulated antibodies are still ongoing. In the interim assessment of the United Kingdom phase III study, elevated levels of efficacy were noted against both the B.1.1.7 variant (vaccine efficacy 86%), and matched prototype-like pre-variant strains (vaccine efficacy 96%). Two other trials have reported vaccine efficacy results against the B.1.351 variant.

In a multi-national phase III study (n=6576), the efficacy of a single dose of vaccine against moderate to severe coronavirus infection was witnessed to be 52% and 64%, 14 days and 28 days after the first dose, respectively, with 95% of cases due to the B.1.351 variant. But, the efficacy of the vaccine against all-severity coronavirus-specific to the B.1.351 variant has not yet been stated, precluding a direct comparison.

In the 2^nd trial, the ChAdOx1-nCoV19 vaccine was assessed in a phase II trial (n=2026) in people with primarily mild to moderate coronavirus infection. The reported vaccine efficacy of 22% overall, and 10% against the B.1.351 variant, with the latter encompassing 95% of the cases.