COVID-19 pandemic has started in December 2019 in China and quickly extended to become a worldwide health and economic emergency issue. It is caused by the novel coronavirus; SARS-CoV-2. COVID-19 patients’ clinical presentations vary from asymptomatic infection or flu like symptoms to serious pneumonia which could be associated with multiple organ failure possibly leading to death. It is understood that the immune response to SARS-CoV-2 includes all elements of the immune system which could altogether succeed in viral elimination and complete cure. Meanwhile, this immune response may also lead to progression of disease and could be responsible for the patient’s death. Many trials have been done recently to create therapies and vaccines against human coronavirus infections such as MERS or SARS, however, till now, no effective antiviral drugs or vaccines have been approved to treat or prevent this disease and its management depends mainly on supportive care. The spike glycoprotein or protein S of SARS-CoV-2 is the main promoter that induces development of neutralizing antibodies; hence, many attempts of vaccines and antiviral drugs development have been designed to be directed specifically against this protein. While some of these attempts have been proved to be efficient in in vitro settings, only few of them have been proceeded to randomized animal trials and human studies which makes Covid-19 prevention an ongoing challenge. This review describes the natural immune response scenario during COVID-19 and the vaccines development trials to create efficient vaccines thus helping to build more effective approaches for prophylaxis and management.